Atherosclerosis

Question 1

what is the primary initiating cause of the development of atherosclerosis?

Answer 1

endothelial injury/damage -

1. lipoprotein enters sub-endothelial space
2. leukocytes are recruited (macrophage)
3. ROS/inflammation follows
4. smooth muscle cells proliferate and ECM is deposited

Question 2

in which vessels does atherosclerosis typically occur?

Answer 2

large/medium muscular arteries

at locations where there is more turbulent flow - ostia of vessels, bifurcation/branch points, regions of high curvature

have “atherogenic” flow patterns (low flow, gradients, flow reversal) that alter endothelial cell phenotype and behavior

Question 3

why does diabetes increase risk of atherosclerosis?

Answer 3

hyperglycemia causes glycation of endothelial cell proteins and lipoproteins —> endothelial damage —> atherosclerosis

Question 4

what are the 5 major risk factors for atherosclerosis?

Answer 4

1. HTN
2. dyslipidemia
3. cigarette smoking
4. diabetes mellitus
5. family history

Question 5

what are the steps of atherosclerosis development?

Answer 5

1. endothelial injury
2. LDL particles enter sub-endothelial and become oxidized
3. macrophage respond to oxidized LDL via scavenger receptor
4. macrophage phagocytose oxidized LDL —> become foam cells
5. foam cells generate inflammatory signaling and recruit more leukocytes
6. smooth muscle cells migrate to intimate and proliferate to create fibrous cap - this sequesters inflammation but narrows lumen

Question 6

how does atherosclerosis plaque rupture occur?

Answer 6

smooth muscle cells form fibrous cap over plaque, but within there is persistent inflammation

inflammatory molecules include metalloproteinases which degrades the plaque, exposes core, and contributes to plaque progression and instability

plaque can rupture, get bigger, and create thrombus

Question 7

when is family history considered a significant for atherosclerosis?

Answer 7

when a first degree relative has coronary artery disease at a young age