PHRD5015 Lecture 13 - Atherosclerosis

pathological process that underlies several important disease states including cerebrovascular disease (stroke) and coronary artery disease (CAD)

involves thickening and hardening of large & medium sized arteries

lesion formed by lipid-rich macrophages lining the walls of the artery

4 changes lesions undergo

causes for endothelial injury

what occurs during endothelial injury

2 cells involved during endothelial injury

macrophages that have absorbed oxidized LDL

lesions with foam cells are extremely common - true/false?
True False

composed of lesions containing foam cells producing ROS and continue to promote damage and sustain an inflammatory response with fibroblasts moving inward

formed when fibroblasts migrate over a fatty streak and combine with collagen produced by proliferating smooth muscle cells

atheroma

distinct regions in which atheroma occur

components of an atheroma

point of growth in the atheroma where inflammatory & immune cells infiltrate and are most abundant

ruptured plaques

formed once a plaque ruptures leading to platelet aggregation and initiation of the clotting cascade

2 major causes of coronary thrombosis

condition in which ruptures preferentially occur

factors secreted by activated inflammatory cells at sites of plaque rupture

break down ECM and weakens plaque cap

2 causes of endothelial erosion by macrophages

protein found on chylomicrons & IDLs, but not LDLs

protein that binds to liver cells and is essential for the uptake and catabolism of fats & cholesterol

phenotype of ApoE-/- mouse

phenotype of LDLR-/- mouse

endothelial damage is associated with _____.

what LDL is primarily comprised of

where LDL in body comes from

increases both with the eating of high fat meals and with the degree of obesity of the individual

cells that can oxidize lipids while using up anti-oxidant defenses

type of LDL taken up by LDLR

response by VECs to MM-LDL

oxLDL receptor

phenotype of ApoE-/- CD36-/- cross

components of oxLDL that bind CD36

first cells to arrive at the site of endothelial activation

important even in disease pathogenesis

predictor of a future cardiac event in human patients with cardiovascular disease

3 steps platelets undergo during the clotting process

3 agonists platelet activation can be mediated by

change in platelets when they are activated

how platelets are activated

component of serum that promotes platelet activation

the ability of platelets to aggregate and bind fibrinogen

factor that can induce platelets to activate

CD36-/- people were (more/less) likely to develop atherosclerosis

M-CSF

macrophages upregulate ____

can activate TLR

activated macrophages upregulate this process, resulting in large amounts of LDL entering the cell

receptors (other than CD36) that can take up oxLDL

response by macrophages when large amounts of cholesterol are taken in

MMP

source of necrotic core found in atherosclerotic plaques

2 factors leading to propensity to generate oxLDL