International Vascular Biology Meeting 2018

President

http://jvbmo.umin.jp/

The Office

The Japanese Vascular Biology and Medicine Organization(JVBMO)

Masayuki Yoshida, MD

The JVBMO supports all vascular-researchers in basic and clinical sciences to perform exciting presentations, deep discussions and free communications. The JVBMO is an Asian representative member for International Vascular Biology Meeting(IVBM).

c/o Proactive Inc. 3F Sannomiya Century Bldg, 83 Kyomachi Chuo-ku, Kobe 650-0034, Japan FAX: +81-78-332-2506 E-MAIL： jvbmo@pac.ne.jp

Copyright © 2018 PerkinElmer, Inc. 400318_15 All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners.

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Contents

Welcome words ..................................................................................6

Committees .........................................................................................8• OrganizingCommittee .................................................................8• LocalOrganizingCommittee ........................................................8• CongressOffice ............................................................................8• InternationalScientificProgramCommittee ...............................9

CollaboratingSocieties .....................................................................11Sponsors ............................................................................................12Exhibitors ..........................................................................................13ExhibitionGuide ................................................................................14

ProgramataGlance .........................................................................16

Program .............................................................................................17

Abstracts ...........................................................................................28• Monday ......................................................................................28• Tue ..............................................................................................78• Wed ......................................................................................... 126

Authorindex .................................................................................. 172

Speakers ......................................................................................... 200

Participants .................................................................................... 206

Wihuri Research Institute (WRI), supported by the Jenny and Antti Wihuri Foundation, is a non-profit biomedical research institute focused on the cardiovascular system in disease. The mission of the Institute is to achieve new fundamental and translational understanding of the

molecular and cellular basis of the vascular system and its involvement in disease pathogenesis, for the benefit of mankind. Discovery and translational research in the Institute

focuses on vascular and regenerative medicine and growth factor signaling mechanisms, using new technologies such as single-cell sequencing and genomic editing of stem cells.

The Jenny and Antti Wihuri Foundation is a DIAMOND SPONSOR of IVBM2018.

Advancing first-in-class treatments targeting the Tie2 Pathway for ocular diseases and diabetes

http://aerpio.com

Dear Colleagues, It is a true pleasure to welcome you to Helsinki for the 20th International Vascular Biology meeting (IVBM2018). IVBM2018 continues the important tradition of bringing together the global vascular biology community to share the newest advancements in the field. Our goal is that the IVBM2018 will present the best vascular biology research from all parts of the world, by researchers of all ages and genders, and promote global exchange of ideas between established and young researchers from academia, clinical medicine and pharmaceutical industry. We are thrilled about the fabulous and diverse list of speakers from all over the world at IVBM2018. We hope that IVBM2018 will bring a lasting impact and promote further breakthroughs and paradigm shifts. We are excited to see many interfaces to other disciplines represented – such as interfaces to immunology, neurobiology and metabolism, just to mention few. This multidisciplinary nature of IVBM2018 highlights the relevance of vascular biology to an increasing number of diseases affecting essentially every organ in our bodies. In IVBM2018, you will see and hear many examples of this, and of many new technologies that allow us to dive deeper into organ-specific vascular diversity in structure and function. We are extremely grateful for the collaboration and partnership of the International Scientific Program Committee in launching the conference. We are also thankful for the Local Organizing Committee for their immense efforts, and members of the local Scientific Crew, who, putting their own research aside, have helped greatly in making IVBM2018 possible and continue serving participants during the meeting. We are tremendously delighted to have our partner societies from all parts of the globe join us in this event. These include the European Vascular Biology Organization, the French Angiogenesis Society, the Japanese Vascular Biology and Medicine Organization, the Korean Society for Vascular Biology and Medicine, the North American Vascular Biology Organization and the Lymphatic Education & Research Network. The support for this meeting has been exceptional, and includes support from institutions, societies, foundations, companies, and organizations. We are most grateful for these partnerships and their generous support. Please take the time to visit the IVBM2018 website (www.helsinki.fi/ivbm2018) to appreciate our many supporters. We are, in turn, dedicated to our partnership with the sponsors in order to organize, support, and facilitate a meeting that will inform, inspire, and foster collaboration. We wish to express our gratitude to all participants of IVBM2018. Your participation will make IVBM2018 an outstanding opportunity to promote collaborations and strengthen our research community. We hope you will enjoy these summer days in Helsinki! - Thank you for joining us at IVBM2018! The Organizing Committee:

Kari Alitalo Christer Betsholtz Lena Claesson-Welsh

Jozef Dulak Pipsa Saharinen Seppo Ylä-Herttuala

Lipedema is a chronic condition that symmetrical buildup of painful fat ad swelling in the arms and legs, sparing the hands and feet. It occurs almost exclusively in women and is poorly understood.

Vascular changes such as telangiectasia are common in lipedema-affected areas, and lipedema may be associated with chronic venous insufficiency.

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Committees

Local Organizing Committee

Michael Jeltsch,PhDAdjunctProfessor,AcademyResearchFellowUniversityofHelsinki&WihuriResearchInstituteHelsinki,Finland

Sinem Karaman,PhD TeamleaderWihuriResearchInstitute&UniversityofHelsinkiHelsinki,Finland

Riikka Kivelä,PhDAcademyResearchFellow,GroupleaderUniversityofHelsinki&WihuriResearchInstituteHelsinki,Finland

Committees

Kaisa Sarkkinen ProjectCoordinatorUniversityofHelsinkiHelsinki,Finland

Laura FellmanSecretaryWihuriResearchInstituteHelsinki,Finland Congress Organiser

Riikka LouhivuoriCongress&EventsManagerConfedentInternationalHelsinki,Finland

Organizing Committee

Kari Alitalo, M.D.,Ph.D.AcademyProfessor,DirectorofWihuriReserachInstituteUniversityofHelsinki&WihuriResearchInstituteHelsinki,Finland

Jozef Dulak, Ph.D.,D.Sc. Professor,HeadoftheDepartmentJagiellonianUniveristyKrakow,Poland

Christer Betsholtz, D.M.Sc. ProfessorinTumorBiologyKarolinskaInstitutet&UppsalaUniversityUppsala,Sweden

Pipsa Saharinen, PhD PrincipalInvestigatorUniversityofHelsinki&WihuriResearchInstituteHelsinki,Finland

Lena Claesson-Welsh, B.D.,Ph.D. ProfessorinVascularBiologyUppsalaUniversityUppsala,Sweden

Seppo Ylä-Herttuala, M.D.,Ph.D.AcademyProfessor,GroupLeaderUniversityofEasternFinlandKuopio,Finland

International Scientific Program CommitteeCommittees

MarcAchen PeterMaccalllumCancerCentre

RalfAdams MaxPlanckInstituteforMolecularBiomedicine

YvonneAlexander ManchesterMetropolitanUniversity

ZoltanArany UniversityofPennsylvaniaHellmutAugustin HeidelbergUniversity&

GermanCancerResearchCenter

AndreaBanfi BaselUniversityHospitalVictoriaBautch TheUniversityofNorth

Carolina-ChapelHillGabrieleBergers Vib-centerforCancerBiologyAndreasBikfalvi InsermJoyceBischoff BostonChildren’sHospital

andHarvardMedicalSchoolTatianaByzova ClevelandClinicMagnusBäck KarolinskaUniversityHospitalElisabettaDejana FircInstituteofMolecular

OncologyMichaelDellinger UtSouthwesternMedical

CenterMichaelDetmar EthZurichAnnaDimberg UppsalaUniversityAnneEichmann YaleUniversityLauriEklund UniversityofOuluUlfEriksson KarolinskaInstitutetAndreasFischer GermanCancerResearch

CenterHolgerGerhardt Max-Delbrueck-Centerfor

MolecularMedicineStephaneGermain INSERMU1050CeciliaGiachelli UniversityofWashingtonNatashaHarvey UniversityofSouthAustraliaYulongHe SoochowUniversityKarenHirschi YaleUniversityTimothyHla BostonChildrensHospital/

HarvardMedicalSchoolBenHogan UniversityofQueenslandYoung-KwonHong UniversityofSouthern

CaliforniaBeatImhof UniversityofGenevaLuisaIruela-Arispe UCLADavidJackson UniversityofOxfordRakeshJain HarvardMedicalSchoolSirpaJalkanen UniversityofTurkuRandallJohnson UniversityofCambridge/

KarolinskaInstituteMinnaKaikkonen-Määttä

UniversityofEasternFinland

SinemKaraman WihuriResearchInstituteandUniversityofHelsinki

DontschoKerjaschki MedicalUniversityofVienna,Dept.Pathology

EliKeshet HebrewUniversityLevonKhachigian UniversityofNewSouth

Wales,SydneyFriedemannKiefer EuropeanInstitutefor

MolecularImaging,WWUMünster

JanKitajewski UniversityofIllinoisatChicago

RiikkaKivelä UniversityofHelsinkiGouYoungKoh Ibs/KaistPetriKovanen WihuriResearchInstituteFerdinandLeNoble KarlsruheInstituteOf

Technology(kit)XuriLi ZhongshanOphthalmic

CenterDonaldMcDonald UCSFNaokiMochizuki Natl.Cerebr.&Cardiovasc.

Ctr.JapanTaijaMäkinen UppsalaUniversityStefaniaNicoli YaleUniversityVesaOlkkonen MinervaFoundationInstitute

ForMedicalResearchGaryOwens UniversityofVirginiaSchool

ofMedicineSamirParikh HarvardMedicalSchool-beth

IsraelDeaconessTatianaPetrova UniversityOfLausanneMichaelPotente MaxPlanckInstituteforHeart

andLungResearchAnnaRandi ImperialCollegeLondonKristyRed-Horse StanfordUniversityYvonneReiss GoetheUniversityHospital

FrankfurtMartinSchwartz YaleUniversityWilliamSessa YaleUniversityMichaelSimons YaleUniversityJean-LeonThomas InsermDietmarVestweber MaxPlanckInstituteof

MolecularBiomedicineMiikkaVikkula DeDuveInstitute,Universite

CatholiquedeLouvainKennethWalsh BostonUniversitySchoolof

MedicineTetsuroWatabe TokyoMedicalandDental

UniversityJunYamashita CenterForIpsCellResearch

&Application,KyotoUniversity,

Ylä-Herttuala,Seppo A.I.VirtanenInstitute,UniversityOfEasternFinland

BinZhou ChineseAcademyofSciencesÖörni,Katariina WihuriResearchInstitute

Collaborating Societies

SponsorsDiamond Level Sponsors

Platinum Level Sponsor

Gold Level Sponsors

Silver Level Sponsors

Contributors and Partners

Exhibitors

Advertisers: 3Scan, Eatris, KDBIO, Labema Oy, Lipedema

Exhibition Guide

Entrance 1st Floor

Ground Floor

Karamzininr

anta

Posters & Exhibition

2nd Floor

Mannerh

eimintie

Lift

Goods lift

Guide display (portrait)

Media display (landscape)

Foyer Level, 2 floornd

Main Building

FINLANDIA HALL-

SOLOIST

ROOMS

ORCHESTRA LOUNGE

HELSINKI HALL

FINLANDIA HALL-( )FOYER PIAZZA

VIP FOYER

HELSINKI HALL-FOYER

RESTAURANT1HALL

RESTAURANT2HALL

RESTAURANT3HALL

1 2 3 4 5 10 20m

28.5.2017 Maarit Loimijoki

IVBM 2018Finlandia Hall3.-7.6.2018

Stand 06ibidid Gmbh

Stand 05

Svanholm.com Aps

Stand 04

Caltag

Medsystems

Stand 03

Bioscientifica

Stand 02

Cell Biologics,

Inc.

Stand 01

Bio-rad

Laborarories Ltd

Stand 07PromegaBiotech Ab

Stand 08Perkin ElmerFinlandOy

Stand 09FujifilmVisualsonics

Stand 16Carl Zeiss Oy

Stand 15Pfizer

Stand 14MoorInstruments Ltd

Stand 13Promocell Gmbh/Biotop Oy

Stand 11Janvier Labs

Stand 10Sartorius

A Brief History of Blood and Lymphatic Vessels

By Andreas Bikfalvi2017. XIII, 192, 9 illu. 52 illu in colour. Softcover.€ (D) 96,29 | € (A) 98,99 | *sFr 99,00ISBN 978-3-319-74375-2€ 74,96 | *sFr 79,00ISBN 978-3-319-74376-9 (eBook)

• Most complete history of our understanding of angiogenesis and vascular biology today

• First conceptual and philosophical analysis in the field • In dept discussion of our current understanding of angiogenesis

and vasculature

This book provides a comprehensive account of vascular biology and pathology and its significance for health and disease. It systematically and chronologically explains how we came to our current understanding of the vasculature and it´s function today, and describes in an entertaining way the diverse flaws and turns in science and medicine from the past.

The first € price and the £ and $ price are net prices, subject to local VAT. Prices indicated with * include VAT for books; the €(D) includes 7% for Germany, the €(A) includes 10% for Austria. Prices indicated with ** include VAT for electronic products; 19% for Germany, 20% for Austria. All prices exclusive of carriage charges. Pricesand other details are subject to change without notice. All errors and omissions excepted.

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Program at a Glance

Monday, June 4, 201808:30–09:50 Plenary session II – Finlandia Main Hall09:50–10:15 Coffee Break

  Helsinki Hall Veranda 1 Veranda 2 Veranda 310:15–12:15 Parallel session 1:

AtherosclerosisParallel session 2: Blood brain barrier

Parallel session 3: TIE2 pathway in vascular disease

Parallel session 4: Metabolic disease

12:15–12:45 Lunch12:30–13:00 Lunch Seminar12:45–14:15 Poster session I - Finlandia Hall Piazza14:15–16:00 Parallel session 5:

Vascular infl ammationParallel session 6: Mechanotrans-duction & ECM

Parallel session 7: Vessel development & stability

Parallel session 8: Lymphatic specifi cation & morphogenesis

16:00–16:30 Coffee Break16:30–17:50 Plenary session III – Finlandia Main Hall18:30 Reception at Helsinki City Hall

Tuesday, June 5, 201808:30–09:50 Plenary session IV – Finlandia Main Hall09:50–10:15 Coffee Break

  Helsinki Hall Veranda 1 Veranda 2 Finlandia Hall10:15–12:15 Parallel session 9:

Neuro-vascular interactions & disease

Parallel session 10: Endothelial cell metabolism & angiogenesis

Parallel session 11: Vascular signalling

Parallel session 12: Targeting tumor vasculature

12:15–12:45 Lunch12:45–14:15 Poster session II - Finlandia Hall Piazza14:15–16:15 Parallel session 13:

Cardiovascular disease

Parallel session 14: Vascular smooth muscle cells

Parallel session 15: Lymphangiogenesis

Parallel session 16: Tumor angiogenesis

16:15–16:45 Coffee Break16:45–18:05 Plenary session V – Finlandia Main Hall

18:10–19:10 Meet the editors

16:30-18:30 ESC round table

18:10–19:10 Showcases  

Wednesday, June 6, 201808:30–09:50 Plenary session VI – Finlandia Main Hall09:50–10:15 Coffee Break

  Helsinki Hall Veranda 1 Veranda 2 Veranda 310:15–12:15 Parallel session 17:

Leukocyte traffi cking & endothelial barrier function

Parallel session 18: Novel functions of lymphatic vessels

Parallel session 19: Angiogenesis

Parallel session 20: Mechanisms of vascular disease

12:15–12:45 Lunch12:45–14:15 Poster session III - Finlandia Hall Piazza14:15–16:00 Parallel session 21:

Organotypic vasculature

Parallel session 22: Endothelial regeneration & senescence

Parallel session 23: Vascular physiology & pathology

Parallel session 24: Epigenetics & genetics of vascular differentiation

16:00–16:30 Coffee Break

16:30–18:50 Plenary session VII & Workshop on Vascular Single-Cell RNA Sequencing – Finlandia Main Hall19:00 Nordic Night at Allas Sea Pool

Thursday, June 7, 2018  Helsinki Hall Veranda 1 Veranda 2 Veranda 3

08:30–09:30 Parallel session 25: Vascular anomalies

Parallel session 26: Clinical translation

Parallel session 27: Arteriogenesis

Parallel session 28: Fluid shear stress regulation

09:30–10:00 Coffee Break10:00–12:30 Plenary session VIII & Poster/Travel award & Closing remarks - Finlandia Main Hall

– 17 –

IVBM2018Program

Sunday, June 3, 2018

17:00-19:30 Plenary session ICo-sponsored by Aerpio Pharmaceuticals - Targeting the Tie2 pathway for novel therapeutics

Finlandia Main HallChairs: Lena Claesson-Welsh, Pipsa Saharinen, Christer Betsholtz & Kari Alitalo17:30-18:10 Napoleone Ferrara (San Diego, CA, USA) Current state of anti-angiogenic therapies18:10-18:50 Susan Quaggin (Chicago, IL, USA) Stolen identities - new vascular phenotypes Tie’d to disease18:50-19:30 Helen Hobbs (Dallas, TX, USA) ANGPTLs, lipid metabolism and energy homeostasis

19:30 Welcome Reception at Finlandia Hall

Monday, June 4, 2018

8:30-9:50 Plenary session IISponsored by Aerpio Pharmaceuticals - Targeting the Tie2 pathway for novel therapeutics

Finlandia Main HallChairs: Hellmut Augustin & Luisa Iruela-Arispe8:30-9:10 Elisabetta Dejana (Milan, Italy & Uppsala, Sweden) Transcriptional regulation of the brain microvasculature9:10-9:50 Gou Young Koh (Daejeon, Korea) Organotypic vasculatures: maintenance and pathophysiology

9:50-10:15 Coffee Break

Parallel sessions 1-4

10:15-12:15 Parallel session 1: AtherosclerosisSponsored by the Japanese Vascular Biology and Medicine Organisation

Helsinki HallChairs: Yvonne Alexander & Petri Kovanen10:15-10:45 Klaus Ley (La Jolla, CA, USA) T cell immune response in atherosclerosis10:45-11:15 Masayuki Yoshida (Tokyo, Japan) A novel role of neutrophils in vascular inflammation and atherosclerosis induced by high fat diet11:15-11:45 Tetsuya Matoba (Fukuoka, Japan) Role of oxysterols in endothelial dysfunction and atherothrombosis11:45-12:00 Short talk: Yun Fang (Chicago, IL, USA) Coronary artery disease locus 1p32.2 harbors a flow-sensitive endothelial enhancer that regulates PLPP312:00-12:15 Short talk: Kim Pin Yeo (Singapore, Singapore) Aortic lymphatic vessel: for or against atherosclerosis in experimental models?

– Sunday – Monday

Program

– 18 –

IVBM2018Program

10:15-12:15 Parallel session 2: Blood brain barrierVeranda 1Chairs: Jean-Leon Thomas & Berislav Zlokovic10:15-10:45 Calvin Kuo (Stanford, CA, USA) Molecular regulation of the blood-brain barrier10:45-11:15 Berislav Zlokovic (Los Angeles, CA, USA) Alzheimer’s disease: A matter of dysfunction of the blood-brain barrier?11:15-11:45 Injune Kim (Daejeon, Korea) Signalings for adult blood-retina barrier maintenance11:45-12:00 Short talk: Patric Turowski (London, UK) VEGF receptor signalling in the leaky neural endothelium12:00-12:15 Short talk: Christian Ramakers (Leiden, The Netherlands) BBB on-a-chip: a 3D in vitro model of the human blood brain barrier (BBB)

10:15-12:15 Parallel session 3: TIE2 pathway in vascular diseaseSponsored by Aerpio Pharmaceuticals - Targeting the Tie2 pathway for novel therapeutics

Veranda 2Chairs: Samir Parikh & Susan Quaggin10:15-10:45 Hellmut Augustin (Heidelberg, Germany) Mechanisms of vascular maturation and quiescence10:45-11:15 Pipsa Saharinen (Helsinki, Finland) New mechanisms of vascular leakage11:15-11:45 Dietmar Vestweber (Münster, Germany) Mechanisms that regulate leukocyte diapedesis and endothelial junctions11:45-12:00 Short talk: Sarah Mueller (Durham, NC, USA) The scaffolding protein Caskin2 regulates vascular homeostasis downstream of Angiopoietin/ Tie receptor signaling11:45-12:00 Short talk: Elizabeth Jones (Leuven, Belgium) Shear stress and VE-cadherin: The molecular mechanism of vascular fusion

10:15-12:15 Parallel session 4: Metabolic diseaseSponsored by Novo Nordisk

Veranda 3Chairs: Zoltan Arany & Kenneth Walsh10:15-10:45 Andreas Fischer (Heidelberg, Germany) Endothelial control of muscle cell metabolism10:45-11:15 Hyo-Soo Kim (Seoul, Korea) Resistin - Cap1 axis in the pathogenesis of metabolic syndrome 11:15-11:45 Ulf Eriksson (Stockholm, Sweden) Role of VEGF-B signaling in diabetic complications11:45-12:00 Short talk: Xuri Li (Guangzhou, China) Novel function of VEGF-B in tethering the FGF2/FGFR1 pathway12:00-12:15 Short talk: Peppi Koivunen (Oulu, Finland) Lower hemoglobin levels associate with lower body mass index and healthier metabolic profile

12:15-12:45 Lunch

– Monday

– 19 –

IVBM2018Program

12:30-13:00 Lunch SeminarSponsored by Aerpio Pharmaceuticals - Targeting the Tie2 pathway for novel therapeutics

Chair: Kevin Peters (Cincinnati, OH, USA)Peter Campochiaro (Baltimore, MD, USA)Targeting the Tie2 pathway for retinal and choroidal vascular diseases

12:45-14:15 Poster session I

Parallel sessions 5-8

14:15-16:00 Parallel session 5: Vascular inflammationHelsinki HallChairs: Jozef Dulak & Dietmar Vestweber14:15-14:45 Beat Imhof (Geneve, Switzerland) Novel mechanisms in acute and chronic vascular inflammation14:45-15:15 Sirpa Jalkanen (Turku, Finland) New tools to prevent vascular leakage15:15-15:45 Britta Engelhardt (Bern, Switzerland) Brain barriers control immune surveillance of the CNS15:45-16:00 Short talk: Jennifer Gamble (Sydney, Australia) Therapeutic manipulation of VE-cadherin

14:15-16:00 Parallel session 6: Mechanotransduction & ECMVeranda 1Chairs: Tatiana Byzova & Claudio Franco14:15-14:45 Stefan Offermanns (Bad Nauheim, Germany) GPCRs and downstream signaling in endothelial mechanotransduction14:45-15:15 Martin A. Schwartz (New Haven, CT, USA) Fluid shear stress in endothelial phenotype and function15:15-15:45 Yu Huang (Hong Kong, China) Endothelial mechanical stress, inflammation and atherogenesis15:45-16:00 Short talk: Anne-Clemence Vion (Nantes, France) Primary cilia sensitize endothelial cells to BMP and prevent excessive vascular regression

14:15-16:00 Parallel session 7: Vessel development & stabilitySponsored by Aerpio Pharmaceuticals - Targeting the Tie2 pathway for novel therapeutics

Veranda 2Chairs: Christopher Kontos & Anna Randi14:15-14:45 Samir Parikh (Boston, MA, USA) Coagulation and hemostasis during inflammation14:45-15:15 Yvonne Reiss (Frankfurt am Main, Germany) Improved survival in a glioblastoma model by a combination of anti-angiogenic and immune checkpoint therapy15:15-15:45 Yulong He (Jiangsu, China) Tie2 in the regulation of angiogenesis and lymphatic formation15:45-16:00 Short talk: Lauri Eklund (Oulu, Finland) Venous specific development and fluid homeostasis in the retina

– Monday

– 20 –

IVBM2018Program

14:15-16:00 Parallel session 8: Lymphatic specification & morphogenesisVeranda 3Chairs: Dontscho Kerjaschki & Taija Mäkinen14:15-14:45 Guillermo Oliver (Chicago, IL, USA) Lumen formation and maintenance in the lymphatic vasculature14:45-15:15 Natasha Harvey (Adelaide, Australia) Dissecting gene function in lymphatic vessel morphogenesis15:15-15:45 Friedemann Kiefer (Münster, Germany) Importance of VE-cadherin in the maintenance of specific lymphatic vessel beds15:45-16:00 Short talk: Michael Jeltsch (Helsinki, Finland) All you ever wanted to know about vascular endothelial growth factor-C processing

16:00-16:30 Coffee Break

16:30-17:50 Plenary session IIICo-sponsored by Aerpio Pharmaceuticals - Targeting the Tie2 pathway for novel therapeutics

Finlandia Main HallChairs: Ralf Adams & Debabrata Mukhopadhyay16:30-17:10 Holger Gerhardt (Berlin, Germany) Principles and regulation of endothelial cell dynamics in angiogenesis17:10-17:50 Naoki Mochizuki (Osaka, Japan) Ang1/Ang2-Tie1/Tie2 signaling for hematovascular development in zebrafish

18:30 Reception at Helsinki City Hall

Tuesday, June 5, 2018

8:30-9:50 Plenary session IVFinlandia Main HallChairs: Jan Kitajewski & Curzio Rüegg8:30-9:10 Anne Eichmann (New Haven, CT, USA), The EMBO Keynote Lecture Guidance of organ-specific vascular patterning9:10-9:50 Rakesh Jain (Boston, MA, USA) Reengineering the tumor microenvironment to improve cancer treatment: Bench to bedside

9:50-10:15 Coffee Break

Parallel sessions 9-12

10:15-12:15 Parallel session 9: Neurovascular interactions & diseaseHelsinki HallChairs: Christer Betsholtz & Britta Engelhardt10:15-10:45 Jaime Grutzendler (New Haven, CT, USA) In vivo optical interrogation of neurovascular function and pathology10:45-11:15 Chenghua Gu (Boston, MA, USA) Interactions of nervous and vascular systems11:15-11:45 Jonathan Kipnis (Charlottesville, VA, USA) Meningeal lymphatic network in CNS pathologies11:45-12:00 Short talk: Bong-Ihn Koh (Daejeon, Korea) Brain photothrombotic injury induces VEGF-dependent pathologic angiogenesis and sustained vascular leakage12:00-12:15 Short talk: Laurent Jacob (Paris, France) Volume imaging of the rachis lymphatic network in rodents

– Monday – Tuesday

– 21 –

IVBM2018Program

10:15-12:15 Parallel session 10: Endothelial cell metabolism & angiogenesisVeranda 1Chairs: Riikka Kivelä & William Sessa10:15-10:45 Zoltan Arany (Philadelphia, PA, USA) The peculiarities of endothelial metabolism10:45-11:15 Michael Potente (Bad Nauheim, Germany) Metabolite signalling in the vascular endothelium11:15-11:45 Peter Carmeliet (Leuven, Belgium) Angiogenesis revisited: role and (therapeutic) implications of endothelial metabolism11:45-12:00 Short talk: Bernard M. van den Berg (Leiden, the Netherlands) Endothelial glucose metabolism regulates glycocalyx hyaluronan synthesis and thereby vessel stability12:00-12:15 Short talk: Debabrata Mukhopadhyay (Jacksonville, FL, USA) Neuropilin-1 maintains dimethylarginine dimethylaminohydrolase 1 expression in endothelial cells and regulates angiotensin II induced-hypertension

10:15-12:15 Parallel session 11: Vascular SignallingSponsored by Eli Lilly

Veranda 2Chairs: Xuri Li & Lena Claesson-Welsh10:15-10:45 Young-Guen Kwon (Seoul, Korea) CLEC14A in regulation of VEGFR-dependent signals in the vasculature10:45-11:15 Tetsuro Watabe (Tokyo, Japan) TGF-β family signals in the formation and maintenance of vascular systems11:15-11:45 Lars Jakobsson (Stockholm, Sweden) Endoglin in regulation of vascular patterning and malformation11:45-12:00 Short talk: Emma Gordon (St. Lucia, Australia) Dynamic cell rearrangements guiding vascular growth and stability12:00-12:15 Short talk: Suk-won Jin (New Haven, CT, USA) ACVR1/ALK2 enables venous selective pro-angiogenic responses to BMP signaling

10:15-12:15 Parallel session 12: Targeting tumor vasculatureSponsored by The Swedish Childhood Cancer Foundation

Finlandia Main HallChairs: Sudhakar Chintharlapalli & Yvonne Reiss10:15-10:45 Michele De Palma (Lausanne, Switzerland) Reprogramming tumor blood vessels for enhancing cancer immunotherapy10:45-11:15 Gabriele Bergers (Leuven, Belgium) High-endothelial venules in cancer11:15-11:45 Donald McDonald (San Francisco, CA, USA) Vascular targeting by oncolytic vaccinia virus11:45-12:00 Short talk: Stephen Moss (London, UK) Pre-clinical development and testing of Magacizumab, a therapeutic antibody against LRG112:00-12:15 Short talk: Radu V. Stan (Hanover, NH, USA) Plasmalemma vesicle associated protein (PLVAP) is a novel target for cancer immunotherapy

12:15-12:45 Lunch

12:45-14:15 Poster session II

– Tuesday

– 22 –

IVBM2018Program

Parallel sessions 13-16

14:15-16:15 Parallel session 13: Cardiovascular diseaseHelsinki HallChairs: Michael Simons & Seppo Ylä-Herttuala14:15-14:45 Riikka Kivelä (Helsinki, Finland) Paracrine regulation of endothelial-cardiomyocyte crosstalk in cardiac hypertrophy14:45-15:15 Kenneth Walsh (Charlottesville, VA, USA) Somatic mutations that drive clonal hematopoiesis and vascular disease15:15-15:45 Stefanie Dimmeler (Frankfurt am Main, Germany) Regulation of vascular growth by non-coding RNAs15:45-16:00 Short talk: Thomas Korff (Heidelberg, Germany) NFAT5/TonEBP - a mechanosensitive transcription factor in vascular smooth muscle cells controlling arterial remodeling16:00-16:15 Short talk: Claudio Franco (Lisbon, Portugal) Junctional forces and wall shear stress compete to coordinate collective endothelial cell polarity

14:15-16:15 Parallel session 14: Vascular smooth muscle cellsOrganized in collaboration with European Society of Cardiology

Veranda 1Chairs: Marie-Luce Bochaton-Piallat & Magnus Bäck14:15-14:45 Cecilia Giachelli (Seattle, WA, USA) Vascular calcification: new concepts in regulation and therapy14:45-15:15 Gordon Francis (Vancouver, Canada) Smooth muscle cells: The silent majority of atherosclerotic lesion foam cells15:15-15:45 Gary Owens (Charlottesville, VA, USA) IL1b signaling in smooth muscle cells plays a critical role in atherosclerotic lesion pathogenesis15:45-16:00 Short talk: Muriel Laffarque (Toulouse, France) PI3Kγ-dependent T cell response delays endothelial healing and reveals a novel role for arterial CXCL1016:00-16:15 Short talk: Angela Bradshaw (Glasgow, UK) TGFβ signaling via ALK1 and ALK5 regulates distinct functional pathways in vein graft intimal hyperplasia

16:30-18:30 European Society of Cardiology round tableVeranda 1

14:15-16:15 Parallel session 15: LymphangiogenesisVeranda 2Chairs: Agnes Noel & Tatiana Petrova14:15-14:45 Taija Mäkinen (Uppsala, Sweden) Mechanisms of sprouting lymphangiogenesis14:45-15:15 Stefan Schulte-Merker (Münster, Germany) Functional analysis of brain lymphatic endothelial cells15:15-15:45 Ben Hogan (Brisbane, Australia) New mechanisms of lymphatic vascular development from zebrafish15:45-16:00 Short talk: Raghu Kataru (New York, NY, USA) Critical role of tumor lymphatic function in regulating tumor inflammatory and immunosuppressive microenvironment16:00-16:15 Short talk: Akira Takeda (Turku, Finland) A new type of lymphatic endothelial cells in the medulla of lymph nodes

– Tuesday

– 23 –

IVBM2018Program

14:15-16:15 Parallel session 16: Tumor angiogenesisSponsored by The Swedish Childhood Cancer Foundation

Finlandia Main HallChairs: Anna Dimberg & Eli Keshet14:15-14:45 Gavin Thurston (Tarrytown, NY, USA) Delta-Notch interactions between stromal cells and tumor cells14:45-15:15 Nobuyuki Takakura (Osaka, Japan) Vascular promotion by LPA4 activation improves the malignant tumor microenvironment15:15-15:45 Kristian Pietras (Lund, Sweden) Blood vessel control of the malignant phenotype15:45-16:00 Short talk: Amanda Lund (Portland, OR, USA) IFNγ-dependent activation of dermal lymphatic vessels limits cytotoxic immunity in malignant and inflamed skin16:00-16:15 Short talk: Giorgio Seano (Paris, France) In vivo dynamics and targeting of vessel co-option in glioblastoma

16:15-16:45 Coffee Break

16:45-18:05 Plenary session VFinlandia Main HallChairs: Stephane Germain & Mark Kahn16:45-17:25 William Sessa (New Haven, CT, USA) The interfaces of endothelial function and lipid metabolism17:25-18:05 Ralf Adams (Münster, Germany) Vascular cell heterogeneity and functional specialization

18:10-19:10 ShowcasesVeranda 218:10-18:40 Pelle Larshammar, Bio-Rad Laboratories Using Droplet Digital™ PCR (ddPCR™) for Cancer and Liquid Biopsy Studies18:40-19:10 Jean Habyarimana, Janvier Labs Breeder’s expertise and its contribution in cardio and vascular research

18:10-19:10 Meet the EditorsHelsinki Hall

Wednesday, June 6, 2018

8:30-9:50 Plenary session VIFinlandia Main HallChairs: Elisabetta Dejana & Vesa Kiviniemi8:30-9:10 Maiken Nedergaard (Copenhagen, Denmark & Rochester, NY, USA) The glymphatic system9:10-9:50 Mark Kahn (Philadelphia, PA, USA) Signaling pathways in vascular disease

9:50-10:15 Coffee Break

– Tuesday – Wednesday

– 24 –

IVBM2018Program

Parallel sessions 17-20

10:15-12:15 Parallel session 17: Leukocyte trafficking & endothelial barrier functionHelsinki HallChairs: Jennifer Gamble & David Jackson10:15-10:45 Cornelia Halin (Zurich, Switzerland) Leukocyte migration through afferent lymphatic vessels10:45-11:15 Jaap van Buul (Amsterdam, The Netherlands) How leukocytes cross the endothelium: the actin link11:15-11:30 Short talk: Masataka Majima (Kanagawa, Japan) Microenvironmental BLT1-signaling facilitates tumor-associated angiogenesis via inducing mast cell recruitment11:30-11:45 Short talk: William A. Muller (Chicago, IL, USA) The role of the PECAM/VE-cadherin/VEGFR2 mechanosensing complex in initiating transendothelial migration11:45-12:00 Short talk: Arie Horowitz (Philadelphia, PA, USA) MPDZ trafficking underlies endothelial cell junction dynamics12:00-12:15 Short talk: Mark Richards (Uppsala, Sweden) Identification of permeability permissive vessels and their molecular markers using correlative intravital imaging

10:15-12:15 Parallel session 18: Novel functions of lymphatic vesselsVeranda 1Chairs: Mark Achen & Jörg Wilting10:15-10:45 Barbara Garmy-Susini (Toulouse, France) Lymphatic system: a novel actor in cancer-associated cachexia10:45-11:15 Ebba Brakenhielm (Rouen, France) Cardiac lymphangiogenesis in cardiovascular diseases11:15-11:45 Dontscho Kerjaschki (Vienna, Austria) Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice11:45-12:00 Short talk: Timothy Padera (Cambridge, MA, USA) Lymph node metastases as a source for distant metastases12:00-12:15 Short talk: Agnès Noel (Liège, Belgium) uPARAP/endo180: a novel partner of VEGFR-2/R-3 that controls VEGF-C-induced lymphatic sprouting

10:15-12:15 Parallel session 19: AngiogenesisVeranda 2Chairs: Holger Gerhardt & Valentin Djonvo10:15-10:45 Victoria Bautch (Chapel Hill, NC, USA) How blood vessels control their destiny10:45-11:15 Yoshiaki Kubota (Tokyo, Japan) Cell-to-cell communication in retinal vascular development11:15-11:45 Rui Benedito (Madrid, Spain) High mitogenic stimulus induced by VEGF or Notch inhibition arrests angiogenesis11:45-12:00 Short talk: Alessandro Fantin (London, UK) Erythro-myeloid progenitors contribute endothelial cells to developing vasculature12:00-12:15 Short talk: Osamu Nakagawa (Osaka, Japan) Significance of the Hey family of transcription factors during cardiovascular development

– Wednesday

– 25 –

IVBM2018Program

10:15-12:15 Parallel session 20: Mechanisms of vascular diseaseVeranda 3Chairs: Andreas Bikfalvi & Karen Hirschi10:15-10:45 Michael Dellinger (Dallas, TX, USA) Lymphatic vessels and vanishing bones: characterization of an animal model of Gorham-Stout disease10:45-11:15 Mariona Graupera (Barcelona, Spain) Role of oncogenic PI3K in endothelium-related diseases11:15-11:45 Goo Taeg Oh (Seoul, Korea) Atherogenesis protection by a novel cytokine produced by alternatively activated macrophages11:45-12:00 Short talk: Andrea Banfi (Basel, Switzerland) EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF12:00-12:15 Short talk: Mia Phillipson (Uppsala, Sweden) Perivascular macrophages regulate blood flow following tissue damage

12:15-12:45 Lunch

12:45-14:15 Poster session III

Parallel sessions 21-24

14:15-16:00 Parallel session 21: Organotypic vasculatureHelsinki HallChairs: Natasha Harvey & Gou Young Koh14:15-14:45 Bin Zhou (Shanghai, China) Genetic targeting of organ specific endothelial cells14:45-15:15 Tatiana Petrova (Lausanne, Switzerland) Organ-specific features and control of lymphatic vasculature15:15-15:45 Karina Yaniv (Rehovot, Israel) Differentiation of endothelial cells and formation of organ-specific vascular beds15:45-16:00 Short talk: Mahak Singhal (Heidelberg, Germany) Endothelial cell fitness dictates the source of regenerating liver vasculature

14:15-16:00 Parallel session 22: Endothelial regeneration & senescenceVeranda 1Chairs: Lauri Eklund & Shahin Rafii14:15-14:45 Jun K. Yamashita (Kyoto, Japan) Blood vessels for tissue regeneration14:45-15:15 Luisa Iruela-Arispe (Los Angeles, CA, USA) Molecular mechanisms of endothelial regeneration15:15-15:45 Mike Sapieha (Montreal, Canada) Cellular senescence and angiogenesis15:45-16:00 Short talk: Mei Xin (Cincinnati, OH, USA) Hippo signaling effector Yap regulates hyaloid vasculature regression in the developing eye

– Wednesday

– 26 –

IVBM2018Program

14:15-16:00 Parallel session 23: Vascular physiology & pathologyVeranda 2Chairs: Timothy Hla & Levon Khachigian14:15-14:45 Ingrid Fleming (Frankfurt am Main, Germany) Inhibition of soluble epoxide hydrolase stabilizes endothelial cell-pericyte interactions and prevents diabetic retinopathy14:45-15:15 Randall S Johnson (Cambridge, UK & Stockholm, Sweden) The role of hypoxic response in vascular function15:15-15:45 Helge Wiig (Bergen, Norway) Extrarenal interstitial sodium storage in extracellular volume and blood pressure homeostasis15:45-16:00 Short talk: Leigh Coultas (Victoria, Australia) ‘Vessel reassembly’ in the absence of endothelial apoptosis as a mechanism for revascularising ischemic retinas

14:15-16:00 Parallel session 24: Epigenetics & genetics of vascular differentiationVeranda 3Chairs: Graeme Birdsey & Risto Kerkelä14:15-14:45 Michael Detmar (Zurich, Switzerland) Epigenetic control of vascular differentiation and function14:45-15:15 Anna Randi (London, United Kingdom) Transcriptional and epigenetic control of endothelial and tissue homeostasis15:15-15:30 Short talk: Stefania Nicoli (New Haven, CT, USA) MicroRNA-dependent regulation of biomechanical genes establish tissue stiffness homeostasis15:30-15:45 Short talk: Minna Kaikkonen-Määttä (Kuopio, Finland) Developmentally regulated chromatin interactions orchestrate transcriptional changes in endothelial cells during vasculogenesis and angiogenesis15:45-16:00 Short talk: Ilse Luyckx (Antwerpen, Belgium) SMAD2 and SMAD6: two novel genetic players in aortic aneurysm and dissection

16:00-16:30 Coffee Break

16:30-18:50 Plenary session VII & WorkshopFinlandia Main HallChairs: Gary Owens & Nobuyuki Takakura16:30-17:10 Michael Simons (New Haven, CT, USA) Disease pathogenesis and cell fate: the tale of two cell types17:10-18:40 Workshop on Vascular Single-Cell RNA Sequencing Investigators from the vascular biology field will present their latest results and discuss technological challenges and bioinformatics methods in single-cell RNA sequencing.17:10-17:40 Sten Linnarsson (Stockholm, Sweden) Inferring cell types and lineages of the mammalian brain from single-cell transcriptomes17:40-17:55 Christer Betsholtz (Uppsala, Sweden) Defining mural cell types by single cell RNA sequencing17:55-18:10 Short talk: Kevin Brulois (Stanford, CA, USA) Single-cell transcriptomics of lymphoid tissue blood endothelial cells18:10-18:25 Short talk: Qi Zhao (Tarrytown, NY, USA) Sequencing tumor endothelial cells with 10x Genomics single cell platform18:25-18:40 Short talk: Michael Vanlandewijck (Uppsala, Sweden) Blood-brain barrier single-cell transcriptomics with SmartSeq218:40-18:50 Presentation of IVBM2020 in Seoul Hyo-Soo Kim & Gou Young Koh

19:00- Nordic Night at Allas Sea Pool

– Wednesday

– 27 –

IVBM2018Program

Thursday, June 7, 2018

Parallel sessions 25-28

8:30-9:30 Parallel session 25: Vascular anomaliesHelsinki HallChairs: Michael Dellinger & Mariona Graupera8:30-9:00 Joyce Bischoff (Boston, MA, USA) GNAQ mutant endothelial cells in capillary malformations9:00-9:30 Miikka Vikkula (Brussels, Belgium) Signaling defects in fast-flow vascular anomalies

8:30-9:30 Parallel session 26: Clinical translationSponsored by Herantis Pharma

Veranda 1Chairs: Andrea Banfi & Michael Detmar8:30-9:00 Seppo Ylä-Herttuala (Kuopio, Finland) VEGFs in therapeutic vascular growth and beyond9:00-9:30 Anne Saarikko (Helsinki, Finland) New therapeutic tools for lymphedema treatment

8:30-9:30 Parallel session 27: ArteriogenesisVeranda 2Chairs: Victoria Bautch & Jun Yamashita8:30-9:00 Kristy Red-Horse (Stanford, CA, USA) Arteriogenesis during cardiac development and injury9:00-9:30 Ferdinand Le Noble (Karlsruhe, Germany) Flt1 determines lumen formation during arteriogenesis

8:30-9:30 Parallel session 28: Fluid shear stress regulationVeranda 3Chairs: Injune Kim & Martin Schwartz8:30-9:00 Young-Kwon Hong (Los Angeles, CA, USA) Regulation of lymphatic development by fluid flow9:00-9:30 Arndt Siekmann (Münster, Germany) Investigating the role of hemodynamic forces in embryonic blood vessel patterning

9:30-10:00 Coffee Break

10:00-12:30 Plenary session VIIISponsored by Regeneron Pharmaceuticals

Finlandia Main Hall

10:00-10:20 Poster/Travel awards ceremony, awards sponsored by LE&RN, NAVBO, EVBO, French Angiogenesis Society, EMBO Molecular Medicine, JVBMO & Wihuri Research InstituteChairs: Naoki Mochizuki & Bin Zhou10:20-11:00 Shahin Rafii (New York, NY, USA) Molecular determinants of vascular heterogeneity development11:00-11:40 Didier Stainier (Bad Nauheim, Germany) Vascular development in zebrafish and mouse11:40-12:20 Timothy Hla (Boston, MA, USA) Signaling and gene expression mechanisms of endothelial injury

12:20-12:30 Closing words

– Thursday

Posters – Monday

– 28 –

IVBM2018

M001

Systematic pharmacological suppression uncovers novel molecular pathways involved in cerebral cavernous malformations

Cécile Otten1, Jessica Knox2,7, Gwénola Boulday3,8, Mathias Eymery4, Martin Neuenschwander5, Ingo Vogt6, Peter Roy2, Corinne Albiges-Rizo4, Eva Faurobert4, Jens von Kries5, Mónica Campillos6, Elisabeth Tournier-Lasserve3,8, Brent Derry2,7, Salim Abdelilah-Seyfried1,91Biochemistry and Biology, Potsdam University, Potsdam, Germany, 2Department of Molecular Genetics, University of Toronto, Ontario, 3Université Paris Diderot, Génétique et physiopathologie des maladies cérébro-vasculaires, Paris, France, 4Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble, France, 5Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany, 6German Center for Diabetes Research, Neuherberg, Germany, 7Developmental and Cell Biology Program, The Hospital for Sick Children, Ontario, Toronto, Canada, 8AP-HP, Groupe hospitalier Saint-Louis, Lariboisière, Fernand-Widal, Service de génétique moléculaire neuro-vasculaire, Paris, France, 9Institute of Molecular Biology, Hannover Medical School, Hannover, Germany

• We screened 5268 unique small-molecules to suppress cerebral cavernous malformation phe-notypes in mutant worm, zebrafish, mouse, or human endothelial cells.

• Systems biology-based target prediction tools revealed signaling pathways relevant to the disease and potential targets for small-mole-cule-based therapies.

• Indirubin-3-monoxime suppressed the loss-of- CCM phenotypes in several CCM mutant models.

M002

Fetal Breathing Movements and Pulmonary Lymphatics Function Together to Prepare the Lung for Inflation

Kitti Ajtay1,2, Mark L. Kahn3, Josef Penninger4, Zoltán Jakus1,2

1Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary, 2MTA-SE „Lendület” Lymphatic Physiology Research Group, Budapest, Hungary, 3University of Pennsylvania, Perelman School of Medicine, Philadelphia, USA, 4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria

• We have revealed the previously unrecognized role of fetal breathing movements (FBMs) in pre-natal lung expansion

• The lack of FBMs results in impaired prenatal pul-monary lymphatic function, while does not influ-ence molecular lung development

• Our results suggest that FBMs and prenatal pul-monary lymphatics function together to prepare the developing lung for inflation at birth

M003

Retinal neurovascular coupling arises at cap-illaries, which show opposite-synchronized responses

Luis Alarcon-Martinez1, Deborah Villafranca-Baughman1, Adriana Di Polo1

1University Of Montreal Hospital Research Center (CRCHUM), Montreal, Canada

• A new approach to study neurovascular coupling in the retina

• Retinal neurovascular coupling occurs at capillary level

• Light-evokedcapillaryresponseareoppositeandsynchronized

M004

Piezo1 and Gq/G11 promote endothelial inflammation and atherosclerosis depending on the flow pattern

Julian Albarran-Juarez1, Till Althoff1,2, Andras Iring1, ShengPeng Wang1, Myriam Grimm1, Boris Strilic1, Nina Wettschureck1,3, Stefan Offermanns1,3

1Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany, 2Charité Department of Cardiology and Vascular Medicine, Berlin, Germany, 3Centre for Molecular Medicine, Medical Faculty, J.W. Goethe University Frankfurt, Frankfurt, Germany

• Piezo1 and Gq/G11-mediated downstream sig-naling processes are involved in endothelial mechanosignaling by primarily sensing flow intensity independently of the flow direction.

• In cells exposed to disturbed flow integrins are activated in a Piezo1-Gq/G11-dependent manner resulting in FAK-mediated NF-kB activation and pro-inflammatory effects.

• Differential activation of integrin signaling by flow represents an important approach to modulate atheroprotection.

Posters

Posters – Monday

– 29 –

IVBM2018

M005

Importance of interplay between endothelial progenitor cells and platelets during athero-sclerosis in a vitro model

Nicoleta Alexandru1, Sabina Frunza2, Emanuel Dragan1, Elisabeta Bãdilã2,3, Alina Constantin1, Miruna Nemecz1, Gabriela Tanko1, Habil Adriana Georgescu1

1Institute of Cellular Biology and Pathology ‘Nicolae Simionescu’ of the Romanian Academy, Bucharest, Romania, 2Internal Medicine Clinic, Emergency Clinical Hospital, Bucharest, Romania, 3’Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania

• In vitro exposure to platelets of healthy origins had a positive effect on functional properties of atherosclerotic late EPCs.

• The most likely candidates mediating EPC-plate-let interaction could be SDF-1alpha, VEGF, PDGF, CD40L, IL-1β,-6,-8, miR-223 and IGF-1R.

• Results lead to new perspective in using EPC for both repair and maintenance of existing vascula-ture within the body, and for cardiovascular dis-ease treatment.

M006

Vascular defects of the retinal vasculature in a mouse model of marfan syndrome

Florian Alonso1, M Thierry Dakhli2, Elisabeth Génot11University Of Bordeaux - Inserm U1045, Bordeaux, France, 2Inserm UMS001, Bordeaux, France

• In Marfan syndrome (MFS), defective fibrillin microfibrils affect elastic and non elastic tissues leading to vascular and ocular defects.

• By confocal imaging on whole mounted retinas from MFS mice, we have identified vascular alter-ations at developmental and adult stages.

• The alterations detected in MFS mouse reti-nas may compromise microvascular functions, thereby contributing to ocular complications.

M007

Investigating the role of Cdc42 in mural cells

Alberto Alvarez-Aznar1, Ralf Adams2, Cord Brakebusch3, Christer Betsholtz1,4, Konstantin Gaengel1

1Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden, 2Max Plank Institut for Molecular Medicine, Department of Tissue Morphogenesis, Münster, Germany, 3University of Copenhagen, BRIC, Copenhagen , Denmark, 4Integrated Cardio Metabolic Centre, Karolinska Institutet, Novum, Huddinge, Sweden

• Deletion of Cdc42 in mural cells using PDG-FR-beta ERT2Cre leads to changes in vascular pat-terning at different developmental stages

• The P7 vasculature appears disorganized with regional changes in vascular density and cross-over of capillaries, this phenotype resolves before P28

• At P28 the vascular branching becomes altered, showing a reduction in branching angles of arte-rioles

M008

Modeling congenital heart disease with patient-derived induced pluripotent stem cells

Minna Ampuja1, Emmi Helle1,3, Diego Balboa2, Solja Eurola2, Tiina Ojala3, Timo Otonkoski2, Riikka Kivelä1

1Research Programs Unit, Translational Cancer Biology Program, Faculty of Medicine, University of Helsinki, and Wihuri Research Institute, Helsinki, Finland, 2Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, Finland, 3Helsinki University Children’s Hospital, University of Helsinki, Helsinki, Finland

• We are studying a new candidate gene variant potentially causing hypoplastic left heart syn-drome (HLHS).

• We generated knockout and heterozygous mutants of the gene in control iPSCs by CRISPR/Cas9.

• HLHS-patient-derived, knockout and heterozy-gous iPSCs were successfully differentiated into cardiac and endothelial cells, which will be used to study the pathogenic role of the gene in HLHS.

Posters – Monday

– 30 –

IVBM2018

M009

Effect of cardiovascular risk factors and heart failure on cardiac endothelial cell transcrip-tome

Karthik Amudhala Hemanthakumar1,2, Shentong Fang1,2, Eero Mervaala3, Riikka Kivelä1,2

1Wihuri Research Institute, Biomedicum Helsinki, Finland, 2Translational Cancer Biology Program, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki, Finland, 3Department of Pharmacology, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Finland

• Effects of exercise training and pathological CVD risk factors (ageing, obesity and TAC) on cardiac endothelial cell transcriptome were studied.

• Exercise increased and pathological stimuli decreased endothelial cell number and all inter-ventions induced significant changes on the car-diac EC transcriptome.

• We have identified genes, which were affected by several treatments, and changed to opposite directions by physiological and pathological stim-uli.

M010

Single cell RNA sequencing studies on peri-cyte-deficient blood-brain barrier

Maarja Andaloussi Mäe1, Liqun He2, Michael Vanlandewijck3, Khayrun Nahar1, Annika Keller4, Christer Bestholtz1,3

1Uppsala University, Uppsala, Sweden, 2Tianjin Neurological Institute, Tianjin, China, 3Karolinska Institute, Stockholm, Sweden, 4Zürich University, Zürich, Switzerland

• Pericyte-deficient Pdgfb ret/ret mouse is a model for several human brain disease-related pro-cesses.

• Single cell RNA sequencing analyses revealed extensive endothelial cell heterogeneity in peri-cyte-deficient brain vasculature.

• Data analysis together with immunofluorescence stainings have been helpful in characterizing the pathologic phenotypes found in pericyte-defi-cient vasculature.

M011

Early developmental induction of vascular mural cell lineage requires Notch signaling

Koji Ando1, Shigetomo Fukuhara2, Naoki Mochizuki3,4, Christer Betsholtz1,5

1Uppsala Univ., Dept. IGP, Rudbeck Lab., Uppsala, Sweden, 2Dept. of Mol. Pathophysiol., Nippon Medical Sch. Japan, Kawasaki, Japan, 3Dept. Cell Biol., Natl. Cerebr. & Cardiovasc. Ctr. Res. Inst., Suita, Japan, 4AMED-CREST, Natl. Cerebr. & Cardiovasc. Ctr. Res. Inst., Suita, Japan, 5Integrated Cardio Metab. Ctr, Karolinska Inst., Huddinge, Sweden

• Description of mural cell (MC) development in zebrafish utilizing MC-reporter lines.

• pdgfrb-high/abcc9+ cells of the MC lineage emerge from peri-arterial naïve pdgfrb-low/abcc9- mesenchymal cells during 36-72 hours post-fertilization.

• Genetic intervention tools revealed that Notch2/3 activation in precursors during differen-tiation periods is indispensable for the differenti-ation into MCs.

M012

Characterisation of perivascular PDGFR-alpha positive mesenchymal cells in meninges and cns

Johanna Andrae1, Michael Vanlandewijck1,2, Maarja Andaloussi Mäe1, Liqun He3, Christer Betsholtz1,2

1Uppsala University, Uppsala, Sweden, 2Integrated Cardio Metabolic Centre/Karolinska Institutet, Huddinge, Sweden, 3Tianjin Medical University General Hospital, Tianjin, China

• Fibroblast-like cells expressing PDGFR-alpha are present along blood vessels in the cns.

• The cells are located between the vascular smooth muscle cells and the astrocyte endfeet.

• 3. Single cell sequencing data imply that there are several subgroups of perivascular fibroblasts.

Posters – Monday

– 31 –

IVBM2018

M013

A new model of guided self-organization allowing rapid formation of functional vessels

Laetitia Andrique1, Gaelle Recher2, Kevin Alessandri2, Nadege Pujol1, Maxime Feyeux2, Pierre Nassoy2, Andreas Bikfalvi1

1Inserm U1029, Pessac, France, 2Institut d’Optique d’Aquitaine LP2N UMR5298, talence, France

• Use of microfluidic device in vascular tissue engi-neering

• Artificial vessels that preserve main properties of mature blood vessels. Revelant model for angio-genesis study.

• Relevant model for vascular graft

M014

Loss of angiopoietin receptor activates YAP/TAZ and a mesenchymal gene set in ECs

Andrey Anisimov1,4, Emilia Korhonen1,4, Pipsa Saharinen1,4, Susan Quaggin2, Marie Jeansson3, Kari Alitalo1,4

1University Of Helsinki, Helsinki, Finland, 2Feinberg Cardiovascular Research Institute and Division of Nephrology and Hypertension, Northwestern University, Chicago, USA, 3Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden, 4Wihuri Research Institute, Biomedicum Helsinki,, Helsinki, Finland

• Tie2 silencing in cultured endothelial cells results in endothelial-to-mesenchymal transition.

• Tie2 silencing led to activation of the major Hippo downstream effectors YAP and TAZ.

• Immunohistochemical analysis of mouse tissues conditionally deleted of Tie2 revealed YAP/TAZ activation and upregulation of the mesenchymal marker vimentin, mirroring the changes upon downregulation of Tie2 at the vascular front in developing retina.

M015

Development and plasticity of meningeal lym-phatic vessels

Salli Antila1, Sinem Karaman1, Harri Nurmi1, Mikko Airavaara2, Merja Voutilainen2, Thomas Mathivet3, Dmitri Chilov1, Zhilin Li1, Tapani Koppinen1, Jun-Hee Park4, Shentong Fang1, Aleksanteri Aspelund1, Mart Saarma2, Anne Eichmann3,5,6, Jean-Léon Thomas4,7, Kari Alitalo1

1Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsinki, Finland, 2Program in Developmental Biology, Institute of Biotechnology, University of Helsinki, P.O. Box 56, Viikinkaari 5D, 00014, Helsinki, , Finland, 3Inserm U970, Paris Cardiovascular Research Center, Paris 75015, , France, 4Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, , USA, 5Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06511, , USA, 6Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, , USA, 7Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS, AP-HP, Institut du Cerveau et de la Moelle Epinière (ICM), Hôpital Pitié-Salpêtrière, Boulevard de l’Hôpital, F-75013, Paris, , France

• Meningeal lymphatic network develops postna-tally

• VEGF-C and VEGFR3 are essential for develop-ment and maintenance of meningeal lymphatic vessels

• Meningeal lymphatic vessels and their function can be modulated with VEGF-C/VEGFR3 pathway also at adult age

Posters – Monday

– 32 –

IVBM2018

M016

Inhibition of endothelial PMCA4 as a novel pro-angiogenic therapy for ischaemic cardio-vascular disease

Sathishkumar Kurusamy1, Dolores Lopez-Maderuelo2,3, Robert Little4, David Cadagan1, Aaron M Savage5, Jude C Ihugba1, Rhiannon R Baggott1, Farjana B Rowther6, Sara Martinez-Martinez2,3, Pablo Gomez-Del Arco2,3,7, Miss Clare Murcott1, Weiguang Wang8, Delvac Oceandy4, Ludwig Neyses4,9, Robert N Wilkinson5, Elizabeth J Cartwright4, Juan Miguel Redondo2,3, Angel L Armesilla1,31Cardiovascular Molecular Pharmacology laboratory, RIHS, School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom, 2Gene Regulation in Cardiovascular Remodelling and Inflammation Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain, 3CIBERCV, , Spain, 4Division of Cardiovascular Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom, 5Department of Infection, Immunity & Cardiovascular disease & Bateson Centre, University of Sheffield, Sheffield, United Kingdom, 6Brain Tumor UK NeuroOncology Research Centre, RIHS, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom, 7Department of Molecular Biology, Universidad Autonoma de Madrid (CBM-SO), Madrid, Spain, 8Oncology Laboratory, RIHS, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom, 9University of Luxembourg, , Luxembourg

• Endothelial Plasma Membrane Calcium ATPase 4 (PMCA4) negatively regulates VEGF-driven angio-genesis via interaction with the signalling protein calcineurin.

• Inhibition of PMCA4 activity in endothelial cells using nanomolar concentrations of the small molecule aurintricarboxylic acid enhances calci-neurin signalling and VEGF-induced angiogenesis.

• 3. Selective inhibition of PMCA4 in endothe-lial cells might be used to improve VEGF-based pro-angiogenic therapeutic interventions.

M017

Loss of Vezf1 impairs β-adrenergic stimuli -induced cardiac growth and contractile func-tion

Jere Paavola1,3, Johanna Ulvila2, Tarja Alakoski2, Teemu Kilpiö2,4, Juuso Sirén1, Sanni Perttunen1, Päivi Lakkisto1,5, Ilkka Tikkanen1,6, Risto Kerkelä2,4

1Unit of Cardiovascular Research, Minerva Institute for Medical Research, Biomedicum Helsinki, Helsinki, Finland, 2Research Unit of Biomedicine, University of Oulu, Oulu, Finland, 3Internal Medicine, Jorvi Hospital, Helsinki University Hospital, Espoo, Finland, 4Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland, 5Clinical Chemistry and Hematology, Helsinki University Hospital, Helsinki, Finland, 6Abdominal Center, Nephrology, Helsinki University Hospital, Helsinki, Finland

• Expression of Vezf1 in the heart is downregulated in human cardiomyopathies

• Zebrafish Vezf1 is necessary for hemodynamic stress –induced cardiac growth and cardiac con-tractile response, and loss of Vezf1 results in greater propensity towards heart failure.

• Molecular analysis for Vezf1 function in cardio-myocytes identifies an MCAT binding site as tar-get for Vezf1.

M018

Extracorporeal application of eddy brakes to control magnetic nanoparticles and modulat-ing the drift and diffusion

Mark Christopher Arokiaraj11Pondicherry Institute Of Medical Sciences, Pondicherry, India

• It is feasible to control the movement of magnetic nanoparticles in the heart using eddy breaks by extracorporeal method.

• Also, the diffusion and drift characteristics of the multifunctional nanoparticles can be modulated.

• Using this ischemia/hypoxic salvage, targeted angiogenesis, modification of endothelial func-tions and changes in cardiac extracellular matrix is feasible.

Posters – Monday

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IVBM2018

M019

Apoproteins modulate tumor angiogenesis and metastasis formation via differential regu-lation of VEGF receptors

Lihee Asaf1, Yogev Sela1, Ifah Raviv1, Yona Eli1, Ehud Zigmond2, Chen Varol2, Karina Yaniv1

1Weizmann Institute Of Science, Rehovot, Israel, 2Research Center for Digestive Tract & Liver Diseases, Sourasky Medical Center, Tel Aviv, Israel

• Lipoprotein levels are inversely correlated with tumor vascularization in LDLR and ApoE KO mice. We uncovered a deleterious role for ApoB100 and ApoE as direct inhibitors of tumor vascular-ization.

• VEGF receptors are downstream targets of apoproteins within endothelial cells, and their endothelial-specific ablation in vivo rescues the anti-angiogenic phenotype.

M020

Collateral and capillary rarefaction is asso-ciated with reduced alternative macrophage activation in type 2 diabetes

Mohan Babu1, Durga Devi Thota1, Minna Kaikkonen1, Petri Mäkinen1, Hanne Laakso1, Timo Liimatainen1, Seppo Ylä-Herttuala1

1Dept of Biotechnology and Molecular Medicine, Aiv Institute, University of Eastern Finland, Kuopio, Finland

• Collateral rarefaction in diabetic muscles is asso-ciated with reduced alternative macrophage acti-vation.

• Diabetic mice display reduced vascularity ratio and increased tissue damage in response to limb ischemia.

• Impaired angiogenesis, reduced endothelial tip cells and endothelial cell proliferation in ischemic muscles is associated with reduced alternative macrophage activation.

M021

MicroRNA-34a promotes senescence-medi-ated vascular smooth muscle cells calcifica-tion by downregulating SIRT1 and Axl

Ileana Badi1, Luigi Mancinelli1, Debora Ferri1, Andrea Polizzotto1, Filippo Zeni1, Ilaria Burba1, Francesca Brambilla2, Claudio Saccu1, Marco E. Bianchi2, Giulio Pompilio1, Maurizio C. Capogrossi3, Angela Raucci1

1Centro Cardiologico Monzino, Milan, Italy, 2IRCCS San Raffaele Scientific Institute, Milan, Italy, 3Ochsner Medical Center, New Orleans, USA

• Mir34a genetic ablation reduces soft tissue and vascular calcification.

• miR-34a promotes vascular smooth muscle cell calcification by inducing cell growth arrest and senescence.

• miR-34a affects the expression of targets, such as Axl and SIRT1, that are vascular calcification inhibitors.

M022

Human IgG1 phosphorylcholine antibody reduces vein graft remodeling, intraplaque angiogenesis, and intraplaque hemorrhage

Fabiana Baganha1,2, Margreet de Vries1,2, Erna Peters1,2, Knut Pettersson3, Paul Quax11,2

1Leiden University Medical Center, Leiden, Netherlands, 2Einthoven Laboratory for Experimental Vascular Medicine, Leiden, Netherlands, 3Athera Biotechnologies, Mölndal, Sweden

• Low levels of natural IgM phosphorylcholine anti-bodies are associated with increased risk for car-diovascular events.

• Intraplaque neovessels are immature resulting in the leakage of circulating cells - intraplaque hemorrhage - leading to an increased cholesterol deposition, atheroma growth, and plaque insta-bility.

• PCmAb, a humanized IgG1 phosphorylcholine antibody, is an effective inhibitor of intraplaque angiogenesis and intraplaque hemorrhage.

Posters – Monday

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IVBM2018

M024

Loss of BMP9 protects against experimental pulmonary arterial hypertension

Ly Tu1,2, Christine Mallet3,4,5, Ayumi Sekine1,2, Jennifer Bordenave1,2, Agnès Desroches-Castan3,4,5, Raphaël Thuillet1,2, Carole Phan1,2, Florian Robert3,4,5, Paul-Benoit Poble1,2, Alice Huertas1,2, Pr Marc Humbert1,2, Christophe Guignabert1,2, Sabine Bailly3,4,51INSERM UMR_999, Le plessis Robinson, France, 2Université Paris-Sud, Université Paris-Saclay, Kremlin-Bicêtre, France, 3U1036, Grenoble, France, 4Univ. Grenoble Alpes, Grenoble, France, 5BIG-Biologie du Cancer et de l’Infection CEA, Grenoble, France

• Heterozygous germline mutations in the BMPR2 gene and more rarely in the ACVRL1 gene have been identified as critical genetic factors predis-posing to PAH.

• The loss of BMP9, by deletion or inhibition, pro-tects rodents against the development of exper-imental PAH.

• BMP9 regulates several factors implicated in the regulation of vascular tone (endothelin-1, apelin and adrenomedullin) that could explain these results.

M025

Integrity of the blood-brain and blood-cere-brospinal fluid barrier in spontaneously hyper-tensive rats

Daphne M. Naessens1, Judith de Vos1, Ed VanBavel1, Erik N.T.P. Bakker11AMC, Amsterdam, Nederland

• Hypertension is an important risk factor for cere-brovascular disease, including stroke and vascular dementia

• We hypothesized that cerebrovascular damage would manifest itself in leakage of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB).

• 3. Surprisingly, we found no evidence for BBB or BCSFB dysfunction in spontaneously hypertensive rat at 10 months of age.

M026

Lymph Flow Mediated Postnatal Remodel-ing of Meningeal Lymphatics Coincides with Beginning of Drainage of Macromolecules

Laszlo Balint1,2, Zsombor Ocskay1,2, Balint Andras Deak1,2, Zoltan Jakus1,2

11, Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary, 22, MTA-SE „Lendület” Lymphatic Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, Budapest, Hungary

• Meningeal lymphatics present in the dura mater are involved in the uptake and transport of mac-romolecules injected into the CNS

• A lymph flow mediated structural remodeling of meningeal lymphatics occurs during the postna-tal period

• Lymph flow mediated postnatal remodeling of meningeal lymphatics coincides with the begin-ning of the drainage of macromolecules from the CNS

M027

EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF

Elena Groppa1, Sime Brkic1, Andrea Uccelli1, Galina Wirth2, Petra Korpisalo-Pirinen2, Maria Filippova1, Boris Dasen1, Veronica Sacchi1, Manuele Muraro1, Marianna Trani1, Silvia Reginato1, Roberto Gianni-Barrera1, Seppo Ylä-Herttuala2,3, Dr Andrea Banfi11Department of Biomedicine, Basel University Hospital, Basel, Switzerland, 2A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland, 3Heart Center, Kuopio University Hospital, Kuopio, Finland

• Therapeutic VEGF delivery to ischemic muscle induces angiogenesis by intussusception (vascu-lar splitting) rather than sprouting

• EphB4 finely tunes the degree of endothelial pro-liferation by specific VEGF doses in vivo, regulat-ing VEGF-R2 signaling output through p-ERK1/2

• Pharmacologic EphB4 stimulation limits the size of initial vessel enlargement, enabling splitting into normal capillaries, and ensures exclusively physiological angiogenesis

Posters – Monday

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IVBM2018

M028

Similarities and differences in the pathology of thoracic aortic aneurysm and the mega-aortic syndrome

Ulrike Baranyi1, Christian Stern1,2, Birgitta Winter1, Adrian Türkcan1,3, Bernhard Scharinger1,3, Marie Teres Stelzmüller6, Thomas Aschacher6, Ass. Martin Andreas6, Ao. Marek Ehrlich6, Günther Laufer6, Ass. David Bernhard4,5, Assoc. Barbara Messner1

1Medical University of Vienna,Department of Surgery, Cardiac Surgery Laboratory, Vienna, Austria, 2Medical Faculty of the Martin Luther University Halle (Saale), Halle , Germany, 3Ludwig Maximilian University Munich, Munich, Germany, 4Innsbruck Medical University,Cardiac Surgery Research Laboratory Innsbruck, Innsbruck, Austria, 5Johannes Kepler University Linz, Center for Medical Research, Linz, Austria, 6Medical University of Vienna, Department of Cardiac Surgery, Vienna, Austria

• Tissues of patients with Thoracic aortic aneu-rysm (TAA) with different luminal size and the mega-aortic syndrome (MAS) were investigated.

• Specimens of the MAS are related to atheroscle-rosis in the ascending aorta compared to speci-mens of TAA tissue.

• Infiltrations of CD68+ macrophages were signifi-cantly elevated in TAA samples and are the main producers of MMP9.

M029

Novel mechanisms underlying the formation of the Blood-Brain Barrier

Ivan Bassi1, Gideon Hen1, Moshe Grunspan1, Karina Yaniv11Weizmann Institute Of Science, Rehovot, Israel

• weakyleak mutant fish display morphological defects in the cerebral vasculature, massive hem-orrhage and bloated lysosomes.

• notch and glut1 downregulation suggest a role for scarb2 in the early stage of BBB development

• weakyleak mutant represent the first in vivo model to investigate the link between lysosome storage disease and BBB breakdown.

M030

Microtubule dynamics in vessel morphogene-sis and homeostasis

Marta Bastos de Oliveira1, Russil Collins1, Holger Gerhardt1,2,3,4

1Max Delbrück Center, Berlin, Germany, 2Vesalius Research Center, VIB, KU Leuven, Leuven, Belgium, 3DZHK (German Center for Cardiovascular Research), Berlin , Germany, 4Berlin Institute of Health , Berlin, Germany

• Cancer patients treated with drugs which interfere with microtubule dynamics exhibit a decrease in tumour vascularisation, which helps their recovery.

• Microtubule growth rate is faster in endothelial cells undergoing angiogenesis than in matured ones.

• Microtubules’ dynamics are necessary for angio-genesis, but not for the maintenance of already formed vessel networks.

M031

Hang on and move – junctional dynamics during vascular morphogenesis

Ilkka Paatero1,3, Loïc Sauteur1, Minkyoung Lee1, Anne K. Lagendijk3, Daniel Heutschi1, Cora Wiesner1, Camilo Gúzman3, Dimitri Bieli Bieli1, Benjamin M. Hogan2, Markus Affolter1, Heinz-Georg Belting11Biozentrum/University Of Basel, Basel, Switzerland, 2IMB, University of Queensland, St Lucia, Australia, 3Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

• We have analyzed dynamics and function of junc-tional components during vascular re- modeling in vivo.

• Morphogenetic EC behaviors are driven by polar-ized and oscillating junction-based la- mellipodia (JBL).

• JBL function as ratchet via VE-cad/F-actin interac-tion and provide the physical means for cell rear-rangements.

Posters – Monday

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IVBM2018

M032

Extracellular vesicle and plaque microRNA-155 expression is dysregulated in human atherosclerotic disease progression

Stephen Ftizsimons1, Niall Mahon2, Nicola Ryan2, Stehpen Sheehan3, Mary Barry3, Orina Belton11Diabetic Complications Research Centre, School of Biomolecular and Biomedical Sciences University College Dublin, Dublin, Ireland, 2Mater Misericordiae University Hospital, Dublin, Ireland, 3St Vincent’s University Hospital, Dublin, Ireland

• Extracellular vesicles (EVs) facilitate cell-to-cell communication and have potential as diagnostic and prognostic biomarkers

• Our data shows that as atherosclerosis pro-gresses there is a decrease in urinary EV con-centration coincident with an increase in both urinary EV and human atherosclerotic plaque miR-155 expression.

• Urinary EV miR-155 expression reflects athero-sclerotic plaque progression and may represent a novel prognostic tool.

M033

Optimizing intra-islet blood vessel formation to enhance an ex vivo Islet-on-a-Chip plat-form

R. Hugh F. Bender1, Matthew Wortham2,3, Bhupinder Shergill6, Kim-Vy Nguyen-Ngoc2,3, Roberto Gaetani5, Karen L. Christman3,5, Steven C. George6, Maike Sander2,3,4, Christopher C.W. Hughes1

1Dept. of Molecular Biology & Biochemistry, University Of California, Irvine, Irvine, United States, 2Pediatric Diabetes Research Center, Dept. of Pediatrics, University of California, San Diego, San Diego, USA, 3Sanford Consortium for Regenerative Medicine, University of California, San Diego, San Diego, USA, 4Dept. of Cellular & Molecular Medicine, University of California, San Diego, San Diego, USA, 5Dept. of Bioengineering, University of California, San Diego, San Diego, USA, 6Dept. of Biomedical Engineering, University of California, Davis, Davis, USA

• Studies on β cell dysfunction in diabetes have his-torically relied on in vitro techniques that fail to maintain islet functionality.

• Our 3D, vascularized, Islet-on-a-Chip platform facilitates functional human islet maintenance for up to two weeks ex vivo.

• We have recently optimized methods for gener-ating islets that form intra-islet vasculature, a key hallmark of islets in vivo.

M034

Genetic Deletion of Telomerase Predisposes for Doxorubicin-Induced Microvascular Dys-function Preceding Development of Heart Failure

Jasmine Linn1,2, Dana Murphy1,2, Matt Hoffman2,3, Laura Norwood Toro1,2, Michael Flister2,3, Andreas M. Beyer1,2,3,41Department of Medicine Medical College Of Wisconsin, MIlwaukee , United States, 2Department of Physiology Medical College Of Wisconsin, MIlwaukee , United States, 3Cardiovascular center Medical College Of Wisconsin, Milwaukee, United States, 4Redox Biology Program Medical College Of Wisconsin, Milwaukee, United States

• TERT KO rats show signs of decreased diastolic heart function

• TERT KO rats have elevated systemic blood pres-sure

• TERT KO rats develop microvascular dysfunction before onset of chemotherapy-induced heart fail-ure

M035

Investigating the role of endothelial cell mor-phology in nitric oxide production

Aparna Bhattacharyya1, Kenneth Barbee11Drexel University, Philadelphia, United States

• Basal eNOS phosphorylation is similar in elon-gated and aligned BAECs and those that are polygonal and randomly oriented.

• ATP, VEGF and bradykinin induce eNOS phosphor-ylation to a greater extent in elongated cells than in polygonal cells.

• Endothelial cell elongation is correlated with increased sensitivity to agonists that modulate eNOS activity

Posters – Monday

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IVBM2018

M036

Cellular and Biomimicking In Vitro Models to Study Capillary Malformations

Colette Bichsel1,2, Lan Huang1,2, Sanda Alexandrescu3, Anna Pinto4, Joyce Bischoff1,2

1Vascular Biology Program, Boston Children’s Hospital and Harvard Medical School, Boston, United States, 2Department of Surgery, Boston Children’s Hospital , Boston, United States, 3Department of Pathology, Boston Children’s Hospital, Boston, United States, 4Department of Neurology, Boston Children’s Hospital, Boston, United States

• Capillary malformations (CM) are caused by somatic mutation in GNAQ in endothelial cells and are associated with novel perivascular acces-sory cells.

• CRISPR/Cas9 was used to introduce the GNAQ point mutation into primary human endothelial cells.

• GNAQ-mutant endothelial cells show decreased proliferation but form vessels with accessory cells in a 3D in vitro microvascular model.

M037

TNIP2: a novel regulator of inflammatory lymphangiogenesis in human atherosclerosis

Marchy Kietadisorn1, Marco Manca1, Timo Rademakers1, Frank Ruehle2, Monica Stoll1,2, Franck Dequiedt3, Judith Sluimer1, Àgnes Noel3, Erik Biessen11University Maastricht, Maastricht, Netherlands, 2University of Muenster, Muenster, Germany, 3University of Liege, Liege, Belgium

• advanced atherosclerosis is typified by major expansion of the lymphactic bed.

• genomics analysis unveils a gene program cor-relating with plaque lymphatics.

• TNIP2 is identified as novel regulator of plaque lymphangiogenesis.

M038

New Insights into PRL2 function in angiogen-esis and arteriovenous differentiation

Mathilde Poulet1,2,3, Jacinth Sirois3, Tiffanie Chouleur1,2,3, Kevin Boye1,2, Serge Hardy3, Thomas Daubon1,2, Noriko Uetani3, Michel Tremblay3, Andreas Bikfalvi1,21Inserm U1029, Pessac, France, 2University Bordeaux, Pessac, France, 3Goodman Cancer Centre - Mc Gill University, Montreal, Canada

• PRL2 is a regulator of vascular development,• PRL2 modulates VEGF and Notch signalling,• PRL2 is involved in arterio-venous differentiation

M039

The role of the long non-coding LINC-PINT in endothelial function

Diewertje Bink1, Patrick Hofmann2, Noelia Lozano Vidal1, Hanjoong Jo3, Stefanie Dimmeler2, Jolanda van der Velden1,4, Reinier Boon1,2

1Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, the Netherlands, 2Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Frankfurt, Germany, 3Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, USA, 4ICIN- Netherlands Heart Institute, Utrecht, the Netherlands

• The long non-coding RNA LINC-PINT is upreg-ulated with age in mouse tissue and primary human endothelial cell lines.

• Knockdown of LINC-PINT with LNA GapmeRs increases apoptosis and reduces proliferation, migration and sprouting in HUVECs.

• LINC-PINT binds to EZH2 and thereby influences gene transcription of P21, ICAM1, VCAM1 and VEGF, affecting endothelial cell function.

M040

The role of long non-coding RNA TERRA in endothelial function

Diewertje Bink1, Patrick Hofmann2, Stefanie Dimmeler2, Jolanda van der Velden1,3, Reinier Boon1,2

1Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, the Netherlands, 2Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Frankfurt, Germany, 3ICIN- Netherlands Heart Institute, Utrecht, the Netherlands

• Long non-coding RNA transcripts called Telomeric repeat-containing RNA (TERRA) are transcribed from the subtelomeres and telomeres of most chromosomes.

• TERRA molecules from different chromosomes are upregulated with age in mouse tissue and pri-mary human endothelial cell lines.

• H20q-TERRA knockdown with LNA GapmeRs shortens telomere length, increases apoptosis and reduces sprouting in HUVECs, affecting endo-thelial cell function.

Posters – Monday

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IVBM2018

M041

The ETS factor ERG controls an endotheli-al-specific transcriptional regulatory program associated with super-enhancers

Viktoria Kalna1, Youwen Yang1, Claire R. Peghaire1, Rebecca Hannah2, Aarti V. Shah1, Lourdes Osuna Almagro1, Joseph J. Boyle1, Jorge Ferrer1, Berthold Gottgens2, Anna M. Randi1, Graeme M. Birdsey11Imperial College London, London, United Kingdom, 2University of Cambridge, Cambridge, United Kingdom

• ERG is essential for endothelial lineage specifi-cation, driving expression of genes such as VWF, CDH5, DLL4, and CLDN5.

• ERG dynamically modulates endothelial enhancers and super-enhancers associated with changes in gene expression.

• ERG is a lineage-determining transcription factor that regulates cell type-specific super-enhancer profiles.

M042

TGF-β regulation of outflow tract development and function in zebrafish

Giulia LM Boezio1, Anabela Bensimon-Brito1, Didier YR Stainier1, Christian SM Helker1

1Max Planck Institute For Heart And Lung Research, Bad Nauheim, Germany

• TgfbrI is expressed in the zebrafish heart (ventri-cle and outflow tract) during larval development.

• CRISPR/Cas9 mutations in TgfbrI lead to a dilation of the heart outflow tract and malformations of the ventral artery.

• The outflow tract dilation in TgfbrI mutant larvae resembles the ascending artery’s defects in TAAD human patients.

M043

Transdifferentiation of human fibroblasts to smooth muscle cells for the study of aortic aneurysm pathology

Natalija Bogunovic1, Dimitra Micha1, Willem Wisselink1, Jan D. Blankensteijn1, Kak K. Yeung1

1Vumc, Amsterdam, Netherlands

• Direct conversion of one mature cell type into another using a growth factor and a specific scaf-fold within fourteen days

• Characterization of smooth muscle cell specific markers on mRNA and protein level, confirming the transdifferentiation into smooth muscle cells

• Application of the method to study pathogenic variants in smooth muscle cell genes causing aor-tic aneurysms

M044

RBMS1: through the eye of angiogenesis.

Rebecca Bolton1, James Brash1, Christiana Ruhrberg11Ucl , London, United Kingdom

• RBMS1 is a nucleic acid-binding protein and a candidate effector of NRP1, a transmembrane receptor with roles in developmental angiogene-sis.

• RBMS1-deletion is embryonic lethal, and endo-thelial cell (EC)-specific deletion of RBMS1 causes defective angiogenesis in the postnatal retina.

• ECs lacking RBMS1 have reduced expression of EC markers and increased expression of mesen-chymal markers, indicative of endothelial-to-mes-enchymal transition.

Posters – Monday

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IVBM2018

M045

Desmoglein-2, an unsuspected regulator of tumour vasculature and immune response in melanoma.

Claudine Bonder1, Lih Tan1, Kay Khine Myo Min1, Michaelia Cockshell1, Jeff Holst2, Michael Brown1, Mark Shackleton3, Lisa Ebert1

1Centre for Cancer Biology, Adelaide, Australia, 2Centenary Institute and the University of Sydney, Sydney, Australia, 3Alfred Health and Monash University, Melbourne, Australia

• tumour growth and metastasis requires access to a blood supply

• desmoglein-2 is a cadherin adhesion molecule that is pro-angiogenic and promotes vasculogenic mimicry in melanoma

• inhibition of desmoglein-2 perturbs cancer growth in vivo by changing the immune response

M046

ABL kinase inhibitor Ponatinib combined with rapamycin causes regression of murine Venous Malformation

Xian Li1, Yuqi Cai1, Jillian Goines1, Elisa Boscolo11Cincinnati Children’s Hospital, Cincinnati, United States

• screening for candidate drugs targeting mutant-TIE2 signaling in venous malformation (VM)

• Ponatinib affects TIE2 and cABL activity down-stream of mutant TIE2

• Ponatinib combined with rapamycin induces regression of mutated-TIE2 derived murinemodel of VM

M047

Hypercholesterolemia promotes a mast cell-CD4+ T-cell interaction in atherosclerosis

Ilze Bot1, Eva Kritikou1, Thomas van der Heijden1, Maarten Swart1, Janine van Duijn1, Bram Slütter1, Harm Smeets2, Anouk Wezel2, Pasquale Maffia3, Johan Kuiper1

1LACDR/Leiden University, Leiden, Netherlands, 2HMC Westeinde, Den Haag, Netherlands, 3Centre for Immunobiology, Institute of Infection, Glasgow, UK

• Upon hyperlipidemia mast cells increase their MHCII expression, present antigens and promote T cell proliferation.

• Human atherosclerotic plaque mast cells express MHCII, suggesting that mast cells may be capable of antigen presentation inside the human athero-sclerotic plaque.

• Mast cells may function as non-classical antigen presenting cells in atherosclerosis.

M048

Preventive effect of Indirubin-3 monoxime on cerebral cavernous malformations (CCM).

Gwénola Boulday1, Cécile Otten2, Mathias Eymery3, Cécile Cardoso1, Coralie De-Luca1, Minh Arnould1, Corinne Albiges-Rizo3, Eva Faurobert3, Salim Abdelilah-Seyfried2, Elisabeth Tournier-Lasserve1,4

1INSERM UMR-1161, Université Paris Diderot, Génétique et physiopathologie des maladies cérébro-vasculaires, Paris, France, 2Institute of Biochemistry and Biology, Potsdam University, Potsdam, Germany, 3INSERM U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, France, 4AP-HP, Groupe hospitalier Saint-Louis, Lariboisière, Fernand-Widal, Service de génétique moléculaire neuro-vasculaire, Paris, France

• IR3mo suppresses CCM phenotype in CCM1-de-pleted HUVEC and CCM2 zebrafish mutant

• IR3mo prevents cerebrovascular lesion develop-ment in both CCM2 and CCM3 mouse models

• IR3mo prevents Klf2 enhanced expression and MAPK activation upon CCM loss in vitro

M049

TGFβ signaling via ALK1 and ALK5 regulates distinct functional pathways in vein graft inti-mal hyperplasia

Emma Low1, Julian Schwartze1, Daniel Kelly1, Sammy El-Mansi1, Andrew Shaw1, Midori Thorikay2, John McClure1, Martin McBride1, Nick Morrell3, Peter ten Dijke2, Andy Baker4, Angela Bradshaw11University Of Glasgow, Glasgow, United Kingdom, 2University of Edinburgh, Edinburgh, United Kingdom, 3Leiden University Medical Centre, Leiden, Holland, 4University of Cambridge, Cambridge, United Kingdom

• TGFβ activates Smad1/5 via ALK1 in SMCs from hyperplastic saphenous vein grafts

• TGFβ signaling via ALK1 in SMCs regulate