Atherosclerosis

Question 1

When does diffuse intimal thickening occur?

Answer 1

Result of injury and natural aging process

Question 2

What happens as a result of injury to the tunica intima?

Answer 2

1. Recruitment of smooth muscle cells

2. Smooth muscle cell phenotype is proliferative / synthetic hence ECM elements are elaborated

Question 3

What is the definition of atherosclerosis?

Answer 3

Form of arteriosclerosis that is characterized by fibrofatty lesions (atheromas) in the tunica intima. These lesions protrude into the vascular lumen thereby producing obstruction and they weaken the tunica media. Obstruction of the vascular lumen leads to ischemia and/or infarction and a weakened media may lead to the development of an aneurysm

Question 4

How many Americans die each year from IHD?

Answer 4

500,000

Question 5

What are nonmodifiable risk factors for IHD?

Answer 5

1. Age (5x incidence 40-60yo)
2. Sex (Men > women until menopause)
3. Family history
4. Genetics (e.g. familial hypercholesterolemia)

Question 6

What are modifiable risk factors for IHD?

Answer 6

1. Cholesterol intake
2. BP
3. Smoking
4. Diabetes
5. Elevated CRP

Question 7

What are the key events in the pathogenesis of atherosclerosis?

Answer 7

1. Injury to endothelial cells
2. Accumulation of lipoproteins
3. Oxidation of LDL
4. Adhesion of blood monocytes
5. Platelet adhesion
6. Growth factor release and recruitment of smooth muscle cells to subendothelium
7. Smooth muscle cell transition from contractile to synthetic
8. Accumulation of lipids

Question 8

What is the effect of CRP on endothelial cells?

Answer 8

Causes them to become pro-thrombogenic and “stickier” for leukocytes

Question 9

What happens when endothelial cells become injured?

Answer 9

1. Become more permeable
2. Synthesize cell adhesion molecules that attach to adluminal plasma membrane
3. Decreased NO production

Question 10

What is the role of LDL when it accumulates post-injury?

Answer 10

Moves across endothelium and enters subendothelial compartment. Macrophages are activated / recruited

Question 11

What oxidizes LDL in the subendothelial compartment?

Answer 11

Endothelial cells, smooth muscle cells, macrophages

Question 12

What occurs as a result of decreased NO?

Answer 12

Increased adhesion of platelets and luekocytes

Question 13

What happens as a result of growth factor release?

Answer 13

Recruitment of smooth muscle cells into subendothelial compartment of tunica intima

Question 14

What types of smooth muscle cells infiltrate the subendothelial compartment following growth factor release?

Answer 14

1. Smooth myocytes from tunica media passing through fenestrae in internal elastic membrane
2. Smooth muscle cell precursors from the blood

Question 15

What are the frequencies of coronary artery narrowing and thrombosis?

Answer 15

1. LAD (40-50%)
2. Right coronary (30-40%)
3. Circumflex (15-20%)

Question 16

What is the wavefront phenomenon of cardiac cell death?

Answer 16

Death occurs in the inner wall of the myocardium (subendomyocardium) and proceeds outward toward the subepicardium

Question 17

What can result from myocardial ischemia?

Answer 17

1. Arrythmias
2. Acute rupture of the cardiac wall or IV septum
3. Rupture of papillary muscles
4. Ventricular aneurysm

Question 18

What are the early (acute) microscopic changes in cerebral infarcts?

Answer 18

Eosinophilia of neurons (red neurons)

Question 19

What happens after eosinophilia of neurons in a CI?

Answer 19

Neutrophil infiltration, then macrophage infiltration (10 days post-injury), then gliosis