How does atherosclerosis develop in terms of appearance and composition of the inner artery? 3
1. Yellow streaks - yellowish raised areas containing cholesterol oleate, smooth muscle cells, foam cells, and fibrous tissue. Present in all children by age 10.
2. Fibrous plaque - grayish raised area sandwich: central core of EC fluid and necrotic cell debris with a fibromuscular cap. Underneath = smooth muscle cells, collagen, macrophages. Cholesterol ester.
3. Complicated lesions - calcified plaques with different amounts of necrosis, thrombosis, and ulceration. Clots form at edge of lesion and platelet aggregation contributes to thrombi formation.
Outcome: Plaques thicken gradually and can occlude the vessel. If arterial wall is weakened, intima can rupture. Emboli can form when plaque fragments dislodge in the lumen.
Describe pathogenesis of atherosclerosis 6 steps
1. Deposits: Due to hypercholesterolemia, deposits of oxidized LDL in endothelium of artery
2. Monocytes --> macrophages: In response to endothelial injury, monocytes adhere to endothelial cells and move to intima --> transformed into macrophages --> inflammation
3. Macrophages --> Foam cells: Macrophages uptake oxLDL and turn into foam cells.
4. Release of growth factors and cytokines --> IL6: Foam cells accumulate, releasing growth factors and cyotkines (interferon gamma, interleukin 1, TNF) inducing prdouction of interleukin6. that stimulate migration of smooth muscle cells from media to intima and become zombies (proliferate, produce collagen, take up lipids and potentially become foam cells)
5. Interleukin 6: stimulates production of thing like CRP6, serum amyloid A and fibrinogenin --> cytokine amplification at each step of the cascade makes downstream measurements of mediators (plasma CRP) useful for diagnosis.