1. Cardiovascular pathophysiology III
BIOL E162a Fall 2009
Cardiovascular pathophysiology III
review section
CO Mendivil, MD

2. ? The endothelium is crucial in initiation of atherosclerosis
Advanced age
Dyslipidemia ?
Hypertension
Diabetes Mellitus
Smoking
Atherosclerosis
Hyperhomocysteinemia
Vascular
endothelium
Chronic inflammation

3. Just “internal lining”=
Just “internal lining”
of blood vessels?
ENDOTHELIUM NO
Vacular tone
Hemodynamic
stimuli
Vascular
proliferation
Endocrine and
Paracrine
secretion
Leukocyte and
PLT adhesion
Thrombogenesis
Thrombolysis
Hormonal
environment
Inflammation

4. Origin of Nitric Oxide Ca++ Ca++ NO Calmodulin Hemodynamic stimuli
Guanilate
cyclase
Ca++
GTP
GMPc
Calmodulin
eNOS
Arginine
Protein
kinase G NO
Hemodynamic
stimuli
Citrulin
Ca++
Hormonal
environment
Relaxation

5. Endothelial dysfunction
Principal característica:
Lower BIOAVAILABILITY of NO
LOWER PRODUCTION
GREATER DEGRADATION
Vasoconstricting hormonal
environment
ADMA
Insulin resistance:
- MAPK inactivation
- eNOS inactivation
Oxidative stress states:
Hypercholesterolemia (cLDL)
Low HDLc
High Angiotensin activity
- High concentration of FFA
Curr Atherosclerosis Rep 2003;5:

6. O2- ON ONOO- Endothelial dysfunction eNOS H2O2
How can oxidative stress induce endothelial dysfunction?
Angiotensin receptor
AT1
NADPH
Oxidase
Xanthine
H2O O2
Glutathion
Peroxidase
Superoxide
Dismutase
(SOD)
XANTHINE
OXIDASE
H2O O2
H2O2
O2-
Catalase
Uric acid
Fe++
OH- ON
ONOO-
eNOS
Endothelium 2003;10:23-33

7. LDLs and endothelial dysfunction
Necrosis
ROS
Apoptosis
LDL
Ox-LDL
Inhibition eNOS
Endothelium 2003;10:17-21

8. Endothelial dysfunction and initiation of atherosclerosis
Remnant
lipoproteins
Monocyte
LDL
Macrophage

9. Initiation of atherosclerosis
Healthy
artery
Fatty
streak

11. The additive effects of LDL and inflammation

12. Expansion of a myocardial infarction

13. How do we detect it ?

14. How do we detect it ? Before Within minutes Within hours Within days
Within years

15. The dreaded image A full-thickness recent myocardial infarction
Elevation of
S-T segment
Inverted
T-wave
Q-wave
with no “r”
A full-thickness recent myocardial infarction

16. How do we detect it ?

17. How do we detect it ?

18. How do we detect it ?
Technecium scan
Resting
Stress

19. How do we detect it ?
Coronary angiography

20. How to prevent them from occurring ?
Controlling risk factors for atherosclerosis:
Lipids
Blood pressure
Glycemia
Smoking
Homocysteine
Body weight - Chronic inflammation

21. Jones PH et al. Am J Cardiol 2003;92:152–160
Statins effectively reduce LDLc
STELLAR study
10mg mg mg mg
Rosuvastatin mg
Atorvastatin mg
Simvastatin mg
Pravastatin mg
-10%
-20%
-30%
-40%
-50%
-60% 20 20 20 20 20 20 20 20 20 20 20 20
n=485 24 24 24 24 24 24 24 24 24 24 24 24 24 28 28 28 28 28 28 28 28
n=648 30 30 30 30 30 30 30 30 30 30 30 30
% LDLc reduction 35 35 35 35 35 35 35 35 35 35 37 37 37 37 37 37 37 37
n=634 39 39 39 39 39 39 39 39 39 39 39 43 43 43 43 43 43 43 46 48 48 48 48 48 48 46 46 46 46 46
n=473 52 52 51 51 51 51 55 55 55
Jones PH et al. Am J Cardiol 2003;92:152–160

23. How to deal with them
once they have occurred ?
Stents

24. Drug-eluting stents

25. How to deal with them once they have occurred ?
Installation of a coronary stent
Before
Installation
After

26. How to deal with them once they have occurred ?

27. What happens later ?

28. Heart failure

29. Heart failure