Covid-19 in the End an Endothelial Disease
Transcript of Covid-19 in the End an Endothelial Disease
Thomas F. Lüscher, MD, FRCP Professor of Cardiology, Imperial College and Director of Research, Education
and Development, Royal Brompton and Harefield Hospital, London, UK
Chairman, Center for Molecular Cardiology, University Zurich, Switzerland
Covid-19 – in the End an Endothelial Disease
Biomarkers & Personalized
Medicine in Cardiology
2021
1.Un (un-)expected Pandemic
2.A Lung Disease
3.Only a Lung Disease?
4.Covid-19 is in the end an Endothelial Disease
5.Covid-19 and Cardiac Injury and Disease
6.CV Collateral Damage of Covid-10
7.Post Covid Disease
1.Un (un-)expected Pandemic
2.A Lung Disease
3.Only a Lung Disease?
4.Covid-19 is in the end an Endothelial Disease
5.Covid-19 and Cardiac Injury and Disease
6.CV Collateral Damage of Covid-10
7.Post Covid Disease
Lung CT Presentation of Covid-19
Typical Features: Multiple bilateral lobular and subsegmental areas of
groundglass opacity or consolidationa, crazy-paving pattern, air bronchograms,
reverse halo/perilobular pattern.
Atypical features: interlobular or septal thickening (smooth or irregular),
thickening of the adjacent pleura, subpleural involvement, pleural effu-sion,
pericardial effusion, bronchiectasis, cavitation, pneumothorax,
lymphadenopathy, round cystic changes.
1.Un (un-)expected Pandemic
2.A Lung Disease
3.Only a Lung Disease?
4.Covid-19 is in the end an Endothelial Disease
5.Covid-19 and Cardiac Injury and Disease
6.CV Collateral Damage of Covid-10
7.Post Covid Disease
Interleukin-6 and serum Amyloid A levels at the site of coronary occlusion and in the
peripheral blood
Interleukin-1a Interleukin-1b
Inte
rleu
kin-
1 Inc
reas
e (%
)
Inte
rleu
kin-
6 (U
/ml)
Baseline Hypoxia
Reperfusion
Y. A
la e
t al.
Agen
ts &
Act
ion
1992
;37:
134-
138
Interleukin-6 and serum Amyloid A levels at the site of coronary occlusion and in the
peripheral blood
Thrombus and Cellular Inflammation at the Site of Plaque Rupture
Immunohistochemistry: CD68 Positive Macrophages (A), IL-6 Positive Staining (B)
Maier, Altwegg et al. Circulation 2005
TF VIIa
Prothrombin Thrombin
Fibrinogen Fibrin
VIIIa
IXa
XII XIIa
XI XIa
IX IXa
Xa X
Ste 2011
vWF
TXA2
ADP
GpIIb/IIIa
PAR-1
Thrombusbildung und Protektion
Aspirin?
Clopidogrel?
Prasugrel?
Ticagrelor?
TNF
(10 ng/mL,
6x10-10 mol/L)
NaCl
(5x10-2 mol/L)
LiCl
(5x10-2 mol/L)
- + + +
- - + -
- - - +
Tissue factor
Tumor Necrosis Factor induces Tissue Factor
in Human Endothelial Cells
47KDa
Western blotting
Eto and Lüscher Circulation 2005
H1
TNF-R
TLR-4 Il-1-R
Histamine
TNF-α
Il-1β
LPS
PAR
Thrombin
KDR
VEGF
CD40
CD40-L
Serotonin
5-HT2a
Inflammation begets Coagulation
TF-bearing
microparticles
asTF
TF pool
Cytoplasm Nucleus
Induction of Tissue Factor Expression
J. Steffel, T.F. Lüscher, F. C. Tanner. Circulation 2005
eNOS
ECE-1
Thrombin (4U/ml, 24h) - + + -
C3 Exoenzyme - - + +
eNOS
ECE-1
Thrombin Regulates Endothelial NOS and ECE-1Expression:
Role of RhoA/ROCK Pathway
Eto et al. Circ. Res. 2001
Thrombin (4U/ml, 24h) - + + -
Y-27632 - - + +
C e l l M e m b r a n e
C y t o s o l
T h r o m b i n
R h o - G D P R h o - G T P
I n a c t i v e A c t i v e
R h o - K i n a s e
eNOS Expression
Tissue Factor
Y - 2 7 6 3 2
Thrombin and Rho/Rho-Kinase Pathway
1.Un (un-)expected Pandemic
2.A Lung Disease
3.Only a Lung Disease?
4.Covid-19 is in the end an Endothelial Disease
5.Covid-19 and Cardiac Injury and Disease
6.CV Collateral Damage of Covid-10
7.Post Covid Disease
Myocardial Injury
• Myocarditis
• Heart Failure
• Hypoxia
• VTE or PE
Myocardial Ischemia
• NSTEMI
• STEMI
• Takotsubo
Cardiac Troponin and Outcome of Acute Covid-19 Infection
1.Un (un-)expected Pandemic
2.A Lung Disease
3.Only a Lung Disease?
4.Covid-19 is in the end an Endothelial Disease
5.Covid-19 and Cardiac Injury and Disease
6.CV Collateral Damage of Covid-10
7.Post Covid Disease
Admission for Myocardial Infarction During Covid-19 Pandemic in Italy Number of Patients admitted in the 12-19 March Week
1.Un (un-)expected Pandemic
2.A Lung Disease
3.Only a Lung Disease?
4.Covid-19 is in the end an Endothelial Disease
5.Covid-19 and Cardiac Injury and Disease
6.CV Collateral Damage of Covid-10
7.Post Covid Disease