1. Dr.Hesham Rashid, MD PATHOGENIC MECHANISMS OF ATHEROSCLEROSIS
Ass.Professor of Cardiology
Benha University

2. Normal Artery

4. GENERAL COMMENTS Arteriosclerosis
Thickening and loss of elasticity of arterial walls
Hardening of the arteries
Greatest morbidity and mortality of all human diseases via
Narrowing
Weakening

5. Three patterns of arteriosclerosis
Atherosclerosis
The dominant pattern of arteriosclerosis
Primarily affects the elastic (aorta, carotid, iliac) and large to medium sized muscular arteries (coronary, popliteal)
Monckeberg medial calcific sclerosis
Arteriolosclerosis –small arteries and arterioles (hypertension and DM)

6. PATHOGENESIS OF ATHEROSCLEROSIS

7. Non-modifiable Risk Factors
Age
A dominant influence
Atherosclerosis begins in the young, but does not precipitate organ injury until later in life
Gender
Men more prone than women, but by age about equal frequency
Family History
Familial cluster of risk factors
Genetic differences

8. Modifiable Risk Factors (potentially controllable)
Hyperlipidemia
Hypertension
Cigarette smoking
Diabetes Mellitus
Elevated Homocysteine
Factors that affect hemostasis and thrombosis
Infections: Herpes virus; Chlamydia pneumoniae
Obesity, sedentary lifestyle, stress

9. The chronic endothelial theory
Two theories have been suggested to explain the onset & progression of atherosclerotic lesions:
The chronic endothelial theory
The lipid hypothesis.
Both theories are interrelated & included in a multifactor-based hypothesis

10. Response to injury hypothesis
* Injury to the endothelium
(dysfunctional endothelium)
* Chronic imflammatory response
* Migration of SMC from media to intima
* Proliferation of SMC in intima
Excess production of ECM
Enhanced lipid accumulation

11. Response to injury hypothesis (I)
1. Chronic EC injury (subtle?)
EC dysfunction
Increased permeability
Leukocyte adhesion (via VCAM-1)
Thrombotic potential

12. Response to injury hypothesis (II)
Accumulation of LDL (cholesterol)
Oxidation of LDL
Adhesion & migration of blood monocytes; transformation into macrophages and foam cells
Adhesion of platelets
Release of factors from platelets, macrophages and ECs

13. Response to injury hypothesis (III)
Migration of SMC from media to intima
Proliferation of SMC
ECM production by SMC
Enhanced lipid accumulation
Intracellular (SMC and macrophages)
Extracellular

14. Response to Injury

15. Endothelial Dysfunction

16. Initiation of Fatty Streak

17. Fatty Streak

18. Fibro-fatty Atheroma

20. AHA Classification of atherosclerosis
                                                                         
                                               
Printed from: Robbins & Cotran Pathologic Basis of Disease (on 11 April 2005) © 2005 Elsevier
AHA Classification of atherosclerosis
Fig

21. AHA Classification of atherosclerosis
                                                                         
                                               
Printed from: Robbins & Cotran Pathologic Basis of Disease (on 11 April 2005) © 2005 Elsevier
AHA Classification of atherosclerosis
Fig

22. Fatty Streak-Coronary Artery

23. Fibrous Plaques
Complicated Lesions

24. ALTERED VESSEL FUNCTION
Vessel change
Plaque narrows lumen
Wall weakened
Thrombosis
Breaking loose of plaque
Loss of elasticity
Consequence
Ischemia, turbulence
Aneurysms, vessel rupture
Narrowing, ischemia, embolization
Athero-embolization
Increase systolic blood pressure

25. Late Changes Calcification Cracking, ulceration, rupture
An example of dystrophic calcification
Cracking, ulceration, rupture
Usually occurs at edge of plaque
Thrombus formation
Caused by endothelial injury,ulceration, turbulence
Organization of thrombus
More thrombus
Encroachment
Weakens vessel wall
Bleeding
Ulceration, cracking and angiogenesis

26. Summary of Atherosclerotic Process
Multifactorial process (risk factors)
Initiated by endothelial dysfunction
Up regulation of endothelial and leukocyte adhesion molecules
Macrophage diapedesis
LDL transcytosis
LDL oxidation
Foam cells
Recruitment and proliferation of smooth muscle cells (synthesis of connective tissue proteins)
Formation and organization of arterial thrombi

28. Thank You