Summer 2010

A Tradition of Excellence

of the

The University of Minnesota cardiovascular program has a legendary history, and has continued to revolutionize and transform cardiovascular medicine.

Welcome to the inaugural issue of our cardiovascular newsletter, Heart of the U. These articles highlight our vision and impact, as the University of Minnesota continues on the road toward discovering a cure for heart disease. The University of Minnesota has a longstanding tradition of cardiovascular excellence, as we are home to the world’s first open-heart surgical procedure, the first to develop and successfully utilize the heart-lung machine, and the first to implant the transistorized pacemaker. These, and numerous other discoveries, have established the University of Minnesota as a leader in cardiovascular research, clinical care, and education. Once again we find ourselves poised to make a significant impact with the goal of becoming a Top 10 cardiovascular program. We recently completed a clinical cardiovascular merger that has established a new care model which will offer our lifesaving innovations to an increasing number of patients. At the same time, we are focusing on our cardiovascular research taking place in the Lillehei Heart Institute and the Cardiovascular Division. The Lillehei Heart Institute is a premier clinical and basic science research

heart The Cardiovascular Newsletter of the University of Minnesota 

UUU

Heart Failure Expert Recruited to Minnesota

Service Line Established to Achieve Cardiovascular Excellence

Research Lab Focuses on Mechanisms of Failing Hearts

700th Heart Transplant!

Molecular Band-Aid Discovered by Cardiovascular Scientists

$170 Million to Support New Stem Cell Initiatives

Getting The Word Out About Heart Disease

Inside this Issue >>> Page 2

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Page 5

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institute focusing on cardiovascular genomics, heart development, heart regenerat ion, s tem-cel l therapies , personalized medicine, heart failure, vascular biology, and device design to treat cardiovascular diseases. As you look through the following pages, you will read about our strategic recruitments, establishment of new programs, state-of-the-art research facilities, and a 250% increase in grant funding (including five large programmatic grants). All of these achievements have led to our unprecedented growth over the last few years. But as we continue to grow, we are reminded that the best predictor of our future is our past. The University of Minnesota cardiovascular program has a legendary history, and has continued to revolutionize and transform cardiovascular medicine. While these developments represent extraordinary investment and expansion in the University of Minnesota cardiovascular enterprise, it takes more than just the University of Minnesota. We encourage you to join our efforts to prevent and cure heart disease, the number-one cause of death in the United States and worldwide.

We encourage you to

join our efforts in

discovering a cure for

heart disease.

Daniel J. Garry, MD, PhD Director, Lillehei Heart Institute Chief, Cardiovascular Division

We are pleased to announce the recruitment of an internationally renowned heart failure expert, Dr. Gary S. Francis, to the University of Minnesota. Dr. Francis was formerly Head of the Clinical Cardiology Section at the Cleveland Clinic and Professor of Medicine at Case Western University. This is Dr. Francis’s second time as a Professor at the University of Minnesota. From 1988 to 1997, Dr. Francis served as a Professor in the University of Minnesota Cardiovascular Division, the Director of Acute Cardiac Care at the University Hospital, and the Research Director for the Rasmussen Heart Center. We were very excited to once again refer to Dr. Francis as a Professor at the University of Minnesota, as he is a nationally recognized leader in internal medicine and cardiovascular diseases, and has been listed in “Best Doctors in America” every year since its inception in the mid-1990s. A few of his other professional accomplishments include serving as president of the Heart Failure Society of America from 2004-2006, being a Fellow of the American College of Cardiology, American Heart Association, and American College of Physicians, as well as being a writing member of the American Board of Internal Medicine in the subspecialty of heart failure and transplantation. Dr. Francis’s main clinical interests are heart failure and acute cardiac care, with the goal of inventing new therapies to prevent heart disease. This interest has allowed him to perform extensive research, including two National Institutes of Health (NIH) Specialized Centers of Clinically Oriented Research (SCCOR) awards. He has also had leadership roles in many national and international clinical trials, and has served on the data and safety monitoring boards of 20 large studies.

Gary Francis, MD, was recruited from The Cleveland Clinic to the University of Minnesota with the goal of inventing new therapies to prevent heart disease.

Faculty Spotlight >>>

World Class Heart Failure Expert Recruited to Minnesota

page 2

In addition to his clinical and research activities, Dr. Francis is a noted educator and author. He was the 1989 and 1991 recipient of the Mentor Award given by University of Minnesota medical students, received national “Master” teaching awards from the University of Miami in 1996 and 2002, and was named “Distinguished Teacher of the Year" at the Cleveland Clinic in 2000. Dr. Francis has also authored or co-authored more than 650 original manuscripts, review papers, editorials, and book chapters, and has edited or co-edited 17 books. He co-authored the 1995, 2001, 2005, and 2008 ACC/AHA heart-failure treatment guidelines, as well as the 2004 AACL guidelines on biomarkers in heart disease and the 2007 NACBLM guidelines on troponin and natriuretic peptides. Dr. Francis has also served as a visiting professor or lecturer at more than 90 universities worldwide. He was the 2006 Laennec Society Lecturer for the American Heart Association, and presented the annual Paul Wood Cardiovascular Lecture at London’s National Heart Hospital in 2008. This year, Dr. Francis’s accomplishments include being appointed editor-in-chief of the Journal of Cardiac Failure, presenting the annual Earl Bakken Lecture at the Cleveland Clinic, and being appointed the third annual Heart Failure Champions Visiting Professor to the Massachusetts General Hospital and Brigham and Women’s Hospital, in Boston, Massachusetts. The addition of Dr. Francis to the Cardiovascular Division at the University of Minnesota enhances our already strong team of physicians and scientists who strive in their effort to cure heart and vascular diseases.

Gary Francis, MD

In October 2008, the University of Minnesota, University of Minnesota Physicians, Minnesota Heart Clinic, and Fairview Health Services established an integrated cardiovascular service line, with the goal of becoming one of the Top 10 cardiovascular programs in the nation. Soon after creating this service line, a two-part strategy evolved to achieve our goal of national excellence in cardiovascular medicine. The first part of the strategy involves implementing University innovation throughout the clinical service line. The second part of the strategy utilizes the geographic reach of Fairview Health Services to create a network of community heart centers throughout Minnesota. Since its inception, our service line has undergone a remarkable transformation. We have added seven cardiologists. Clinics at our anchor hospitals [the University of Minnesota Medical Center (UMMC) and Fairview Southdale Hospital] have expanded the scope of services offered and patient volumes, while visits to our outreach clinics have grown by more than 40%. Coronary Structural & Interventional (CSI), a UMMC inpatient service dedicated to coronary and structural disease, offers rapid triage and treatment for patients with acute coronary syndromes, and the UMMC cardiac catheterization laboratory has experienced a 20% volume increase. In addition, clinical research studies have increased by 66%.

Service Line Established to Achieve Cardiovascular Excellence

Clinical Update >>>

Robert Wilson, MD

New Appointments Robert Arpke Postdoctoral Associate Natarajan Bhanu Postdoctoral Associate John Casnovsky Student Lab Assistant Sunny Sun-Kin Chan Postdoctoral Associate Joseph DeCock Information Tech Nazanin Dolatshad, PhD Postdoctoral Associate Kristen England, PhD Postdoctoral Associate Stephanie Espersen Office & Administrative Specialist Holger Fey, PhD Postdoctoral Associate Lindsy Halleckson Office & Administrative Specialist Cara-Lin Lonetree Assistant Scientist Hallie Magrew Office & Administrative Specialist Travis Maher Graduate Student Allison Nelson Undergraduate Student Jai Prakash Richard, PhD Postdoctoral Associate Andrew Rosenbaum Research Assistant Danielle Rux Junior Scientist Tory Schaaf Junior Scientist Andrea Silverman Administrative Director Katelynn Splett Science/Engineering, Entry Level Katrina Tollefsrud Senior Lab Technician Erik Toso Junior Scientist Kevin Tram Scientist Nolan Turner Student Lab Assistant Camille Walter Student Lab Assistant Peter Eckman, M.D. Assistant Professor Suma Konety, M.D. Assistant Professor Carolina Masri, M.D. Assistant Professor

We are confident

we will have the

area’s largest

cardiovascular

program, with

innovative care

and geographic

reach across

Minnesota.

While this transformation is remarkable, we have much more to do to achieve our goal. This quarter, we began the process of integrating interventional cardiology services across the entire program. This effort involves physicians, nurses, our three cardiac catheterization laboratory sites, research groups, quality systems, information systems, materials management, finance, and marketing. When interventional integration is complete, we intend to have the area’s largest interventional program, providing innovative cardiovascular care and geographic reach across the state of Minnesota. Integration of imaging, electrophysiology, heart failure, and preventative cardiology will follow as the year unfolds. At the same time as we organize our clinical services delivery, it is critical that we develop an infrastructure for clinical innovation, including: internal seed grants to enable early investigation of faculty-generated ideas, pre-clinical facilities for device development and testing, clinical cell-therapy laboratories, clinical research space adjacent to care-delivery areas, and a clinical trials nursing unit. As you can see, the face of the University of Minnesota Physicians cardiovascular program is changing. We need your continued support to deliver our promise to be the best.

Robert Wilson, MD Professor of Medicine Executive Medical Director, UMP Cardiovascular Service Line page 3

Faculty Recruitments

Summer Research Scholars Program Begins Second Year

With the goal of encouraging medical and scientific careers in cardiovascular medicine, the Lillehei Heart Institute announces its annual summer research scholarships. These competitive and notable awards are designed to expose highly-qualified students to several disciplines within cardiovascular medicine. Every scholar will be supported by a named research scholarship. Each major project focus will be intensive basic or clinical research, as each scholar will be assigned a laboratory and a faculty mentor. In addition, scholars will be introduced to academic, clinical, and industrial medicine through a variety of field trips, seminars, and hands-on experiences.

Awards >>>

University of Minnesota Scientist Honored for Research Excellence

On March 12th, the University of Minnesota Medical School and t h e M i n n e s o t a M e d i c a l Foundation announced that Michael Kyba, PhD, Assistant Professor in the Lillehei Heart Institute, was the 2010 recipient of the Dr. Marvin and Hadassah Bacaner Research Award in Cardiovascular Biology. This award, presented yearly since 1978, recognizes excellence in

David Benditt, MD, Professor in the Cardiovascular Division, was recently designated a Fellow of the European Society of Cardiology (FESC) by the European Society of Cardiology. Fellowship in the European Society of Cardiology is an internationally-recognized and honored position that distinguishes clinical cardiologists and cardiovascular scientists who have a deep interest and knowledge of the clinical, educational, investigational, organizational, and professional aspects of cardiovascular medicine. FESC designation is currently bestowed upon only 2,943 cardiologists and nurses throughout the world. Dr. Benditt was also recently named a “Top Doctor” in the Twin Cities area by the Mpls/St. Paul magazine.

World Class Electrophysiologist

Receives International

Award

Postdoctoral fellow Antonio Filareto and undergraduate student Sarah Parker, both of Dr. Rita Perlingeiro’s laboratory, were awarded a Gregory Marzolf Jr. Muscular Dystrophy Training Grant. Presented annually by the University of Minnesota’s Paula and Sheila Wellstone Muscular Dystrophy Center, Marzolf training grants are intended to improve educational experiences for undergraduate, graduate, and professional students interested in the areas of basic and clinical muscle research.

Two Receive Prestigious Marzolf Grants

David Benditt, MD

Michael Kyba, PhD

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2009 Summer

Research Scholars

creative basic science research and represents an investment in the careers of outstanding and promising investigators at the University of Minnesota. Previous award winners include Cindy Martin, MD,(2009), and Yingjie Chen, PhD, (2008). Both have positions within the Lillehei Heart Institute.

Research Lab Focuses on Mechanisms of Failing Hearts

Featured Research Lab >>>

Twin Cities Start! Heart Walk Celebration Held June 5th

Hundreds of people showed up on June 5, 2010, for the annual Start! Heart

Walk, sponsored by the American Heart Association (AHA). Through this

event, the AHA encourages people to improve their health by walking, while

simultaneously raising funds for lifesaving research and public education to

fight heart disease and stroke. This year’s event has held at the Minnesota

Twins’ new Target Field. Walkers organized teams with co-workers, family,

and friends. For more information on the Twin Cities Start! Heart Walk, visit

http://twincitiesheartwalk.org.

Yingjie Chen, PhD, Assistant Professor

in the Cardiovascular Division, and his

laboratory are currently using

experimental approaches (including

modifying selective genes in cultured

cells, generating state-of-the-art tissue-

specific gene-modified mouse models,

and analyzing integrated cardiovascular

function in experimental subjects) to

identify molecular targets associated

with abnormal mitochondrial biogenesis

and funding from the National Institutes

of

700th Heart Transplant!

Target Field, in Minneapolis, MN, was

the site of this year’s Start! Heart Walk.

On February 2, 2010, the University of Minnesota heart transplantation program reached a significant milestone by performing its 700th heart transplant at the University of Minnesota Medical Center, Fairview. Our heart transplant program is world-renowned for leading-edge therapies such as using mechanical circulatory support to bridge patients to transplant, and applying innovative uses of antirejection drug therapies. Last year the program performed 31 heart transplants with an outstanding one-year survival rate of 95%. For a video celebrating this event, visit http://www.mmf.umn.edu/heart/.

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A life-saving surgery marks a major milestone

for the University of Minnesota Heart

Transplantation Program.

Ranjit John, M.D., transplant surgeon, Cindy Martin, M.D., cardiologist, and

Kenneth Liao, M.D., transplant surgeon

Yingjie Chen,

PhD

and ventricular dysfunction in the failing heart. The Chen

laboratory is currently focused on cell-specific functions of

dimethylarginine dimethylaminohydrolase 1 (DDAH1) and

translational initiation on cardiovascular function.

Dr. Chen’s research efforts have attracted attention. In 2008, he

was awarded the Dr. Marvin and Hadassah Bacaner Research

Award in Cardiovascular Biology at the University of

Minnesota, and recently received approximately $500,000 of

grant funding from the National Institutes of Health (NIH) and

the American Heart Association (AHA).

In the March 15th edition of the Washington Post, Michael Kyba, PhD, Assistant Professor in the Lillehei Heart Institute, spoke about new stem cell guidelines that could effect the choice of stem cell lines. Kyba’s laboratory at the University of Minnesota is using the most popular of the original stem cell lines, known as H9, to study how stem cells “morph” into specific tissues. In addition to these cell lines, the Kyba laboratory is generating human pluripotent stem cells (iPSC’s) from patient’s skin cells. For more information on this story, visit the Washington Post online at http://www.washingtonpost.com/.

Benefits of SHIP Discussed in the

Minnesota Senate On February 24th, Courtney Jordan, MD,

Clinical Fellow in the Cardiovascular

Division, testified before the Minnesota

Senate Health and Human Services Budget

Division on the importance of continuing

the Statewide Health Improvement Plan

(SHIP). Dr. Jordan, Chair of the SHIP

healthcare workgroup, is involved in

changing policy and protocol to prevent

obesity across Minnesota. The SHIP

healthcare workgroup has been

instrumental in implementing activities to

create environments conducive to healthy

body weight and decreased tobacco use.

The SHIP program is being implemented

by city, county, and tribal public health

departments across Minnesota. For more

i n f o r m a t i o n , v i s i t h t t p : / /

www.health.state.mn.us/healthreform/

ship/.

In the News >>> Stem Cell Biology

Discussed in Washington Post

Early Intervention is a Key to Preventing Diabetes

Daniel Duprez, MD, Professor in the Cardiovascular Division, was quoted in News Blaze regarding a study suggesting that many patients at pre-diabetes and pre-hypertension levels may be at risk for cardiovascular disease. Dr. Duprez stated that his findings strengthen the case for early intervention: "We recommend noninvasive screening for patients with prediabetes to detect cases of early cardiovascular disease, when patients may be likely to respond to lifestyle changes and effective pharmacotherapy," Duprez says.

Daniel Duprez,

MD, PhD

page 6

Dr. Duprez’s research interests include arterial mechanics and stiffness, biomarkers for early cardiovascular disease, lipoproteins, neurohormonal factors and hypertension, HIV and cardiovascular disease, and clinical-trials events evaluation. Dr. Duprez is the Donald and Patricia Garofalo Chair for Preventive Cardiology and the Director of Research in the Rasmussen Center for Cardiovascular Disease Prevention. For more information on this story, visit http://newsblaze.com/story/2010050223591300012.wi/topstory.html.

Stay current with cardiovascular news and events at the University of Minnesota!

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ONLINE!

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http://twitter.com/HeartoftheU

Molecular Band-Aid Discovered by University of Minnesota Cardiovascular Scientists

ask the experts >>>

Women’s Heart Health Summit a Success

Providers in women’s health, primary care,

emergency medicine, and cardiovascular

disease and prevention attended this

groundbreaking initiative.

On April 29-30, the first Women’s Heart Health

Summit was held at the Marquette Hotel in

downtown Minneapolis. Presented by the

Minneapolis Heart Institute Foundation, the

Minneapolis Heart Institute, the Mayo Clinic,

and the University of Minnesota, this summit

assembled experts to help identify and address

gender inequalities in heart disease. The first

day’s program featured keynote addresses and

panel discussions with 12 national experts and

20 regional leaders. On the second day, “think-

tank” discussions were held to formulate actions

needed to improve diagnosing and treating heart

disease in women. Four areas of major focus

were identified:

National community initiatives:

Awareness and prevention

Symptom recognition and treatment

delays: Clinical and social factors

Closing the survival gap: Differences in

biology, pathophysiology, treatment, and

outcomes

Patient-provider connection: Challenges

for women with heart disease, secondary

prevention, and disease management

For more information on this event, visit http://

www.mplsheart.org/.

Researchers at the University of Minnesota Medical School, including Joseph Metzger, PhD, (Professor and Chair of the Department of Integrative Biology and Physiology), DeWayne Townsend, DVM, PhD (Assistant Professor in the Department of Integrative Biology and Physiology), and colleagues have discovered a chemical that may protect the hearts of patients with

Transplant Survival Rates Among the Nation’s Best

In 2009, the University of Minnesota Medical Center (UMMC) was again among the nation’s leading programs in heart transplantation. Our transplant center performed 31 adult heart transplants, with a one-year patient survival rate of approximately 95%. On February 2, 2010, we performed our 700th heart transplant.

In addition to having heart-transplant survival rates that are among the nation’s best, the UMMC Transplant Center is also a national leader in ventricular-assist device (VAD) therapy for patients with severe end-stage heart disease. We have performed approximately 500 VAD implants. For more information, visit the UMMC Transplant Center website at http://www.uofmtransplant.org.

Joseph Metzger, PhD,

and DeWayne

Townsend, DVM, PhD

Duchenne Muscular Dystrophy from the long-term effects of their disease. The chemical, which the scientists call a “molecular band-aid,” seeks out defects (tiny cuts) in diseased heart muscle. When injected into the bloodstream, the molecular band-aid finds these microscopic defects (cuts) and protects them from harmful substances so that heart-muscle cells survive and function normally. In order to be effective, the chemical must be repeatedly injected, similar to the way a diabetic patient requires regular injections of insulin. For more information, visit http://www.ahc.umn.edu/media/releases/molecularbandaid.

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Clinical Faculty Members Awarded Funding

Benditt, David: Astellas Pharma US, Inc. Phase 3b Study of Vernakalant Injection, $36,815 Chen, Yingjie: NIH. DDAH1 Effects on the Development of Congestive Heart Failure, $415,250 Colvin-Adams, Monica: American Heart Association. Evaluation of Phosphodiesterase-5 Inhibition on Endothelial, $110,000 Das, Gladwin: Schering-Plough Corporation. Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome, $162,444 Eckman, Peter: NIH. Xanthine Oxidase Inhibition for Hyperuricemic Heart, $96,400 Garry, Daniel: NIH, Midwestern Progenitor Cell Consortium, $7,927,500 Garry, Mary: NIH. The Exercise Pressor Reflex in Cardiomyopathy, $1,887,500 Hall, Jennifer: Minnesota Medical Foundation. Lineage-Specific Telemetry for Measuring Arterial Blood Pressure in Mice, $17,000

This year marks the first time that the University of

Minnesota Cardiovascular Division has awarded funding

to their own clinical faculty members for

professional growth in the area of clinical research. In March, 2010, it was announced that six clinical faculty members in the Cardiovascular Division were awarded division funding for professional growth in the area of clinical research. These grants were awarded on the basis of scientific merit and other conventional criteria including career stage, mentoring strength, and other considerations as determined by an internal committee. Clinical faculty members who received awards include Drs. David Benditt, Lin Chen, Monica Colvin-Adams, Peter Eckman, Cindy Martin, and Demetris Yannopoulos. Each award is $75,000 per year for a duration of 12-24 months. Since the intent of this funding is to encourage professional growth, awardees are also expected to apply for external grant support (i.e., NIH, AHA, etc.) to continue their research.

Research Awards >>>

New Grant Awards Exceed $14 Million

Huo, Yuqing: American Diabetes Association. Macrophage A2A Receptor Regulates Glucose Homeostasis, $333,500 Kyba, Michael: NIH. Lineage-Specific Reprogramming to Blood, $354,349 Kyba, Michael: NIH. FSHD iPS Cells: Modeling Disease Mechanisms, $1,625,412 Martin, Cindy: NIH. Etsrp71-Regulated Networks of Cardiovascular Development, $500,000 Perlingeiro, Rita: Minnesota Medical Foundation. MMF Equipment Grant: Stereomicroscope, $6,000

Perlingeiro, Rita: NIH. Examining the Therapeutic Potential of iPS cells in Duchenne Muscular Dystrophy, $999,659 Raveendran, Ganesh: Minneapolis Heart Institute Foundation. Cardiovascular Cell-Therapy Research Network, $11,988

Rita Perlingeiro, PhD, Associate Professor in the Cardiovascular Division and the Lillehei Heart Institute, was recently awarded a challenge grant from the National Institutes of Health (NIH) for a project titled “Examining the Therapeutic Potential of iPS Cells in Duchenne Muscular Dystrophy.” This $1 million grant funds a two-year project focusing on the myogenic differential potential of mouse-induced pluripotent stem (iPS) cells, human embryonic stem (ES) cells, and their therapeutic application for degenerative diseases.

Funding Facilitates Stem Cell Research

Rita Perlingeiro, PhD

Our cardiovascular research funding has increased by 250% over the last three years due to increased

emphasis on discovery and innovations. Here are grant awards received since July 2009:

page 8

ask the experts >>>

The University of Minnesota is the co-recipient of a collaborative $170M programmatic award involving 18 institutions and focusing on emerging technologies, including induced pluripotent stem cell biology. This award is titled the Midwestern Progenitor Cell Consortium, and has a goal of identifying and characterizing progenitor cell lineages, as well as directing the differentiation of stem and progenitor cells to desired cell fates, and developing new strategies to address the unique challenges presented by the transplantation of these cells. Dr. Daniel Garry, Director of the Lillehei Heart Institute and Chief of the Cardiovascular Division, is the lead Principal Investigator (PI) of this grant and states that the projects undertaken at the University will define the key regulatory nodes in the networks that promote stem cells and progenitor cells to adopt a hematopoietic and cardiovascular cell fate – with an aim toward improving clinical options. We will decipher the intracellular, extracellular, and paracrine factors that promote stem/progenitor cell specification and differentiation to cardiac, vascular, and hematopoietic restricted lineages. In these projects, we will utilize an array of tools and emerging technologies including transgenic mouse models, genetically engineered embryonic and induced pluripotent stem cells, clonal cardiac progenitor cell populations, the decellularized heart, and state-of-the-art high resolution imaging/spectroscopy technologies. These tools and technologies will facilitate our studies and those of our partners at the University of Wisconsin and others associated with the consortium. The overall goal of this proposal is to mechanistically decipher the intracellular and extracellular networks that govern specification and differentiation of stem cells to the cardiovascular and hematopoietic lineages. This consortium has assembled clusters of synergistic research projects, each with a multi-disciplinary team of Principal Investigators, to establish virtual Research Hubs focused on progenitor cell biology. These investigators include Dan Kaufman, M.D., Ph.D., Michael Kyba, Ph.D., Jonathan Slack, Ph.D., Doris Taylor, Ph.D., and Jianyi Zhang, M.D., Ph.D.

$170 Million to Support New Stem Cell Initiatives at the

University of Minnesota

Grant Aims to Study Inflammation and Cardiovascular Disease

Yuqing Huo, PhD, Assistant Professor in the Cardiovascular Division and the Lillehei Heart Institute, recently received a grant from the American Diabetes Association (ADA) f o r a p r o j e c t t i t l e d “Macrophage A2A Receptor R e g u l a t e s G l u c o s e Homeostasis.” A three-year project funded for $333,500, Dr. Huo’s study focuses on the inflammatory aspect of cardiovascular diseases. Specifically, it seeks to define the mechanisms underlying the role of adenosine receptor 2A (A2AR) i n r e g u l a t i n g g l u c o s e homeostasis.

Michael Kyba, PhD, Assistant Professor in the Lillehei

Heart Institute, received grant funding from the National

Institutes of Health (NIH) to study Facioscapulohumeral

Muscular Dystrophy (FSHD). FSHD is a common and

debilitating neuromuscular disease for which there is no

treatment. Although the genetic mutation that causes

FSHD has been identified, the mechanism leading to the

disease is not understood.

Using pluripotent stem cells derived from FSHD patient

cells, Dr. Kyba’s research will expand our molecular

understanding of FSHD and potentially lead to a genetic

therapy.

Yuqing Huo, PhD,

uncovers the

inflammatory

aspects of heart

disease.

Michael Kyba, PhD

Researcher Looks to Cure Debilitating Neuromuscular

Disease

page 9

Clinical Trial Evaluates New Therapy in

Patients with Acute Coronary Syndrome

Gladwin Das, MD, Associate Professor in the Cardiovascular Division and the Lillehei Heart Institute, has been awarded funding from the Schering-Plough Corporation for a clinical trial to determine whether a study drug (SCH 530348), when added to the existing standard of care (e.g. aspirin and clopidogrel) for preventing heart attack and stroke in patients with acute coronary syndromes, will yield additional benefit. The study is also designed to assess bleeding with SCH 530348 when added to the standard of care. For more information on this clinical trial, contact research nurse Aimee Hamel by phone at (612) 626-4726, or by e-mail at muehl010@umn.edu.

Clinical Trials >>>

Heart Failure Specialist Receives Clinical Trial Funding to Study Allopurinol

Peter Eckman, MD, Assistant Professor in the Cardiovascular Division and the Lillehei Heart Institute, was recently awarded clinical-trial funding from the National Institutes of Health (NIH) to study the use of allopurinol in patients with symptomatic heart failure due to left-ventricular systolic dysfunction and elevated serum uric-acid levels. His hope is that allopurinol, which has been on the market since 1964 to treat excess uric acid in blood plasma, can also be used to control the uric acid levels of patients with heart failure. For more information on this clinical trial, contact research nurse Aimee Hamel by phone at (612) 626-4726, or by e-mail at muehl010@umn.edu.

Peter Eckman, MD

Gladwin Das, MD

National Grant Award Received by U of M Physician–Scientist

Cindy Martin, MD, Assistant Professor and Lillehei Heart Institute researcher, was recently awarded a Clinical Scientist Development Award (CSDA) grant from the National Institutes of Health (NIH). This grant will fund a five-year, $500,000 project titled “Etsrp71-Regulated Networks of Cardiovascular Development” that seeks to advance understanding of transcriptional cascades and signaling pathways during embryogenesis. NIH CDSAs provide support and “protected time” to individuals with clinical doctoral degrees for intensive, supervised research career-development experiences in the fields of biomedical and behavioral research, including translational research. Dr. Martin’s CDSA grant will allow her to continue translating her in-vitro preliminary data to in-vivo transgenic models, and provide opportunities to begin applying her scientific findings to clinical practice.

Cindy Martin, MD, seeks to

further our understanding of

heart development and

congenital heart disease.

page 10

Implementing the 2005 American Heart Association Guidelines Improves Outcomes after Out-of-Hospital Cardiac Arrest. Aufderheide TP, Yannopoulos D, Lick CJ, Myers B, Romig LA, Stothert JC, Barnard J, Vartanian L, Pilgrim AJ, Benditt DG. Heart Rhythm. 2010 Apr 23. PGC-1 alpha regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload. Lu Z, Xu X, Hu X, Fassett JT, Zhu G, Tao Y, Li J, Zhang P, Zhao B, Chen Y. Antioxid Redox Signal. 2010 Apr 21. Oxidative stress regulates left ventricular PDE5 expression in the failing heart. Lu Z, Xu X, Hu X, Lee S, Traverse JH, Zhu G, Fassett J, Tao Y, Zhang P, dos Remedios C, Pritzker M, Hall JL, Garry DJ, Chen Y. Circulation. 2010 Apr 6;121(13):1474-83. Detecting the patient at risk of heart failure. Cohn JN. J Am Coll Cardiol. 2010 May 11;55(19):2138-9. Effects on pre- and post-transplant pulmonary hemodynamics in patients with continuous-flow left-ventricular assist devices. John R, Liao K, Kamdar F, Eckman P, Boyle A, Colvin-Adams M. J Thorac Cardiovasc Surg. 2010 Apr 30. Arterial stiffness and endothelial function: key players in vascular health. Duprez DA. Hypertension. 2010 Mar;55(3):612-3. Epub 2010 Jan 18.

Getting the Word Out About Heart Disease

Publications >>>

Does baseline carotid intima-media thickness modify the effect of rosuvastatin when compared with placebo on carotid intima-media thickness progression? The METEOR study. Crouse JR 3rd, Bots ML, Evans GW, Palmer MK, O'Leary DH, Grobbee DE, Raichlen JS; METEOR Study Group. Eur J Cardiovasc Prev Rehabil. 2010 Apr;17(2):223-9. Structural and functional vascular alterations and incident hypertension in normotensive adults: the Multi-Ethnic Study of Atherosclerosis. Peralta CA, Adeney KL, Shlipak MG, Jacobs D Jr, Duprez D, Bluemke D, Polak J, Psaty B, Kestenbaum BR. Am J Epidemiol. 2010 Jan 1;171(1):63-71. The year in heart failure. Tang WH, Francis GS. J Am Coll Cardiol. 2010 Feb 16;55(7):688-96. A resuscitation of bretylium? Yannopoulos D, Garry DJ. Am J Ther. 2009 Nov-Dec;16(6):480-1. Genetic mutations as risk predictors of atrial fibrillation recurrence after catheter ablation? Hall JL, Barac A, Benjamin EJ. J Am Coll Cardiol. 2010 Feb 23;55(8):754-7. Acadesine inhibits tissue factor induction and thrombus formation by activating the phosphoinositide 3-kinase/Akt signaling pathway. Zhang W, Wang J, Wang H, Tang R, Belcher JD, Viollet B, Geng JG, Zhang C, Wu C, Slungaard A, Zhu C, Huo Y. Arterioscler Thromb Vasc Biol. 2010 May;30(5):1000-6.

No assisted ventilation cardiopulmonary resuscitation and 24-hour neurological outcomes in a porcine model of cardiac arrest. Yannopoulos D, Matsuura T, McKnite S, Goodman N, Idris A, Tang W, Aufderheide TP, Lurie KG. Crit Care Med. 2010 Jan;38(1):254-60. Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction. Jameel MN, Li Q, Mansoor A, Qiang X, Sarver A, Wang X, Swingen C, Zhang J. Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1348-56. Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs. Townsend D, Turner I, Yasuda S, Martindale J, Davis J, Shillingford M, Kornegay JN, Metzger JM. J Clin Invest. 2010 Apr;120(4):1140-50. doi: 10.1172/JCI41329. Combinatorial effects of double cardiomyopathy mutant alleles in rodent myocytes: a predictive cellular model of myofilament dysregulation in disease. Davis J, Metzger JM. PLoS One. 2010 Feb 10;5(2):e9140.

In the first quarter of 2010, Lillehei Heart Institute investigators published more than 65 peer-reviewed journal articles. Representative publications include:

page 11

University of Minnesota

Cardiovascular Division & Lillehei Heart Institute

Department of Medicine

Medical School

420 Delaware Street SE

MMC 508

Minneapolis, MN 55455

http://www.med.umn.edu/cardiology/

http://www.med.umn.edu/lhi/

June 9th Lillehei Heart Institute Lecture Series

Kevin Campbell, PhD

University of Iowa

University of Minnesota

Mayo Auditorium

June 10th Fellowship Graduation

University of Minnesota

McNamara Alumni Center

June 24th-26th Cardiovascular Program Annual Retreat

Saint John’s University, Collegeville, MN

Events... Upcoming June 26th Matters of the Heart:

Cells, Stress, Wine, and Chocolate

University of Minnesota, St. Paul Campus

July 6th Stethoscope Ceremony

University of Minnesota

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