17 Atherosclerosis

Question 1

State modifiable and non modifiable risk factors that are associated with atherosclerosis

Answer 1

Modifiable: Obesity, diabetes, blood pressure, lipid, lack of exercise and cigarette smoke

Non-modifialbe: sex, genes, age

Question 2

True of false: atherosclerosis develops continuously

Answer 2

False, step wise

Question 3

State the main cell types and their function in the development of atherosclerosis

Answer 3

1) Vascular endothelial cells: Barrier function (eg to lipoproteins), Leukocyte recruitment
2) Platelets: Thrombus generation, Cytokine and growth factor release
3) Monocyte-macrophages: Foam cell formation, Cytokine and growth factor release, Major source of free radicals, Metalloproteinases
4) Vascular smooth muscle cells: Migration and proliferation; Collagen synthesis; Remodelling and fibrous cap formation
5) T lymphocytes: Macrophage activation

Question 4

What is the role of LDL in atherosclerosis

Answer 4

LDL leaks through the endothelial cells and becomes stuck to the subendothelial proteoglycans where it is susceptible to modification by oxidative stress

Question 5

What is the fate of oxLDL

Answer 5

oxLDL contributes to the formation of foam cells from macrophages. Uptake of oxLDL by scavenger receptors expressed on macrophages SR-A (CD204) and SR-B (CD36)

Question 6

What are the 4 main roles of macrophages

Answer 6

1. Generates free radicals to modify trapped LDL into oxLDL (NADPH oxidase/myeloperoxidase)
2. Uptake of oxLDL by SR-A and SR-B and become foam cells
3. Become activated and express:
   
   • Cytokines (MCP-1 and IL-1)
   • Chemokines and growth factors for VSMC (PDGF and TGF - increase collagen synthesis and matrix deposition)
   • Proteinases (MMP
   • Tissue factors for thrombosis
     4) Die by apoptosis

Question 7

What are the characteristics of vulnerable plaque

Answer 7

1. Size of necrotic core
2. Expression of MMP from macrophages
3. Collagen synthesis from VSMC
4. VSMC apoptosis
5. Thin fibrous cap

Question 8

What is the characteristics of endothelial erosion

Answer 8

1. Independent of necrotic core size
2. Non-occlusive thrombosis
3. Loss of endothelial cells
4. Increasing as portion of plaque destablisation
5. Loss of endothelial cells