Lecture 19/20: Atherosclerosis

Question 1

What are the 3 cardiovascular effects?

Answer 1

1) plaque formation: decreases vessel radius, vasodilator reserve reduced
2) plaque rupture: exposes collagen, creates clotting
3) increased risk of embolism: thrombus forms, can block vessel

Question 2

How do we know lipids are involved?

Answer 2

Epidemiology studies (Framingham), genetic disorders (mutation in protein allowing cholesterol to bind HDL), family studies (mutation in receptor, increased risk), transgenic mice (more LDL = cardiovascular disease), pharmocological interventions (statins: inhibit HMG-CoA reductase, prevents cholesterol synthesis, also anti-inflammatory)

Question 3

What are some diagnostic indicators of atherosclerosis?

Answer 3

1) c-reactive protein: released from liver in response to cytokines
2) presence of bacteria/viruses
3) hyperhomocysteine: associated with oxidative stress
4) Lipoprotein A
5) increased blood iron concentration
6) platelet aggregation: more susceptible to clotting/thrombus
7) erectile dysfunction: decrease in endothelial function
8) peridontal disease: chronic inflammatory state

Question 4

Describe the oxidized LDL hypothesis?

Answer 4

LDL slips into intima layer, gets oxidized by reactive oxidative radicals released from endothelial cell. attaches to scavenger receptors on mast cells, absorbed, mast cells turn into foam cells. release several factors, increase expression of VCAMs, causes adhesion of more mast cells and t-cells. T-cells clean up dead endothelial cells but also destroy smooth muscle cap. foam cell attracts smooth muscle precursors/cell from lumen and media layer by releasing cytokines
also activates matrix metalloproteinases that destroy sm cap, contact with collagen triggers clotting.

Question 5

Describe the how hypertension, diabetes, and inflammation is linked to atherosclerosis

Answer 5

hypertension = more turbulent, non-laminar flow, more stress on cells, so more likely to be damaged and expose collagen, increase monocyte adhesion

diabetes: unable to utilize glucose, therefore lots of oxidation of LDL
inflammation: increased cytokine levels, increased matrix metalloproteinases

Question 6

Discuss pharmocological interventions

Answer 6

Statins: decrease HMG-coA reductase, anti-inflammatory
folic acid: decreases level of homocysteine
aspirin: vasodilator
antihypertensive: ACE inhibitor, beta blocker
niacin: fixes HDL:LDL ratio

Question 7

Discuss surgical interventions

Answer 7

can have stent inserted, or bypass
stent can have restenosis
bypass can have new atherosclerosis, if using a vein, not well-suited for high pressure out of heart