AtherosclerosisAtherosclerosis
Atherosclerotic Cardiovascular Disease (ASCVD)
Smooth m. proliferation Endothelial injury Lipids (cholesterol)
Pathogenesis of atherosclerosis
1 Normal Artery Structure
Lipoprotein particle
2 XX 60,00060,000 xx 180,000180,000
Robert Hamilton, Ph.D. EM: Negative staining Cardiovascular Research Inst., UCSF
3 The cholesterol in LDL accounts for ©Medscape approx. 70% of the plasma cholesterol
Arteriosclerosis (Hardening of the arteries)
Arterial wall thickening + loss of elasticity Monckeberg medial Arteriolosclerosis Atherosclerosis calcific sclerosis
hyaline
hyper- plastic
¾Age 50 -small arteries/arterioles -aorta & branches + ¾Radiologic calcif. -hyaline type / hyperplastic coronary arteries ¾Lumen intact -hypertension / diabetes -ASCVD causes 38% of ¾Clinically insignif. all deaths in N. America
4 ATHEROSCLEROSIS: response-to-injury model
Atherosclerosis is a chronic inflammatory response of the arterial wall to endothelial injury. 1. Chronic endothelial injury
2. Accumulation of lipoproteins (LDL mainly) basic tenets 3. Monocyte adhesion to endothelium 4. Platelet adhesion 5. Factors releasedÆSMC recruitment 6. SMC proliferation and ECM production 7. Lipid accumulation: extracellular/mac-SMC
Risk Factors for Atherosclerosis
•Hypertension
•Turbulence
•Genetics
5 Endothelial injury
Early Chronic—repetitive injury non- denuding endothelial dysfunction
-cig. smoke toxins -homocysteine -?? Infectious agents -cytokinesÆgenes for
Endothelial injury
Early Chronic—repetitive injury non- denuding endothelial dysfunction
-cig. smoke toxins 1. Hemodynamic -homocysteine disturbances -?? Infectious agents (turbulence) 2. Hypercholesterolemia 3. Inflammation
6 Endothelial injury
Early Chronic—repetitive injury non- denuding endothelial dysfunction IEM
-cig. smoke toxins 1. Hemodynamic -homocysteine disturbances -?? Infectious agents (turbulence) 2. Hypercholesterolemia Smooth muscle proliferation: 3. Inflammation - proliferative & synthetic phenotype in intimal SMC’s (vs. SMC in media) - growth factors: PDGF, FGF, TGFα
Pathogenic sequence of atherosclerotic lesions
7 Normal aorta
Fatty streak
Atheromatous plaque (fibrofatty plaque)
Complicated plaque
8 Fatty Streaks
Atheromatous plaque (fibrofatty atheroma; plaque; atheroma)
9 Complicated plaque: ulcerated/thrombus
Aneurysm
10 Thrombus in aneurysm
ATHEROSCLEROSIS: Vessel involvement: desc. order 5 circle of Willis vessels 4 internal carotid a’s
Ao 2 Cor. A’s 1 abd. aorta
3 popliteal a’s
11 Development of the smooth muscle cap
Atherosclerostic Plaque Structure
12 AA IELIEL MM ECEC
13 14 15 16 17 18 Natural history of atherosclerosis
Robbins 8/e
Atherosclerosis (AS): Summary
1. AS is an intima-based lesion with a fibrous cap and atheromatous (gruel-like) core 2. Constituents: SMC’s, ECM, inflamm., lipid, necrotic debris 3. Endothelial injury + inflammation drive AS: risk factors influence EC dysfunction, SMC recruitment and activation 4. AS plaque complications: rupture—thrombosis—hemorrhage— embolization 5. Rx: risk factor recognition + reduction
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