The document discusses atherosclerosis and its risk factors and various hypotheses about its pathogenesis. It describes the roles of oxidized LDL, macrophages, and endothelial cells in driving atherosclerosis. It outlines the progression from fatty streaks to more advanced atheromatous plaques and complicated lesions. Fatty streaks are the earliest subclinical lesions while atherosclerosis refers to lesions that are clinically significant. Complications can arise from processes like calcification, ulceration, rupture, hemorrhage, and thrombosis.

1. ATHEROSCLEROSIS

2. RISK FACTORS FOR ATHEROSCLEROSIS

3. ATHEROGENIC HYPOTHESES
Insudation hypothesis
Encrustation hypothesis
Reaction to injury hypothesis
Monoclonal hypothesis
Intimal cell mass and neointima
formation hypothesis
Hemodynamic hypothesis

4. UNIFYING HYPOTHESIS

5. ROLE OF OXIDIZED LDL IN ATHEROGENESIS
1) Readily ingested by macrophages
2) Chemotactic for circulating monocytes
3) Increases monocyte adhesion
4) Inhibits motility of macrophages
5) Favours recruitment and retention of macrophages
6) Stimulates release of growth factors and cytokines
7) Cytotoxic to endothelial and smooth muscle cells
8) immunogenic

6. ROLE OF MACROPHAGE IN ATHEROGENESIS
MACROPHAGE
IL-1 , TNF , and MCP-1
Increases adhesion of leukocytes
Toxic oxygen species
Oxidation of LDL
Growth stimulators & inhibitors
Modulate the proliferation of SMCs
Deposition of ECM protiens

7. ROLE OF ENDOTHELIAL CELL IN ATHEROGENESIS
 Increase in the permiability of the wall to lipoprotiens
 Acceleration of lipoprotien accumulation
 Permit platelet interaction with the vessel wall
 Subsequent release of growth factors
 Allow the formation of thrombus on the surface
 Neovascularization in the shoulders of fibrous caps

8. PDGF NO
bFGF PGI2
IL-1 IGF-1
TGF ox LDL
Endothelial cell
Antigens
PDGF EGF
TGF α TGF β
TxA2 IGF-1
PLASMA
Angiotensin
LDL

10. FATTY STREAK
ATHEROMATOUS PLAQUE
 FIBROUS
 FIBROFATTY
 LIPID
 FIBROLIPID PLAQUES
COMPLICATED PLAQUE

16. FATTY STREAK
Fatty streaks are the earliest lesions of Atherosclerosis
Fatty streaks are flat or slightly elevated lesions
Contain accumulations of intracellular and
extracellular lipid in the intima
Found in young children as well as adults
Cells filled with lipid droplets ( foam cells )
Mostly macrophages and few smooth muscle cells also
contain fat droplets

17. Do not correspond to the distribution of athero-
sclerotic lesions in adults
Fatty spots are common in thoracic aorta but
atherosclerosis commom in abdominal aorta
Fatty infiltration represents the initial lesions of
atherosclerosis
Atherosclerosis - clinically significant lesions
Fatty streaks are not significant clinically

24. COMPLICATED ATHEROSCLEROSIS
CALCIFICATION
ULCERATION
FOCAL RUPTURE ( Atheroemboli )
HEMORRHAGE
SUPERIMPOSED THROMBOSIS
ANEURYSMAL DILATION

25. COMPLICATIONS
Acute occlusion
Chronic narrowing of vessel lumen
Aneurysm formation
Embolism