W.7b: Atherosclerosis

Question 1

Definition of arteriosclerosis

Answer 1

General term describing any hardening (and loss of elasticity) of medium or large arteries

Question 2

Definition of arteriolosclerosis

Answer 2

Any hardening (and loss of elasticity) of arterioles. Often due to hypertension and/or DM

Question 3

Definition of atherosclerosis

Answer 3

Hardening of any artery specifically due to an atheromatosus plaque formation

Question 4

Clinical manifestations of atherosclerosis (3 main)

Answer 4

1. Coronary heart disease (54%) - angina, MI, sudden cardiac death
2. Cerebrovascular disease (18%) - transient ischemic attacks, stroke
3. Others (17%) - peripheral vascular disease, aortic aneurysm, renal a. stenosis, mesenteric occlusion

Question 5

What are the symptoms of acute mesenteric ischemia?

Answer 5

• Sharp, postprandial pain
• Nausea and/or vomiting
• Bloody stool
• A-fib and/or cardiomyopathy

Question 6

Characteristics of unstable plaques

Answer 6

A lipid core with a thin fibrous cap that can cause endothelial dusfunction, erosions and thrombus

Question 7

Characteristics of stable plaques

Answer 7

A lipid core with a thick fibrous cap

Question 8

Non-modifiable risk factors of atherosclerosis

Answer 8

• Age (dominant influence)
• Gender (men more prone than women)
• Family history (risk factors, genetic differences)

Question 9

Modifiable risk factors of atherosclerosis

Answer 9

• Hyperlipidemia, hypertension
• Smoking
• DM
• Elevated homocysteine
• Factors that affect hemostasis and thrombosis
• Infections: Herpes virus, Chlamydia pneumoniae
• Obesity, sedentary lifestyle, stress

Question 10

What is the content of the necrotic center of a plaque?

Answer 10

Cell debris, cholesterol crystal, foam cells, calcium

Question 11

What is the content of the fibrous capsule of a plaque?

Answer 11

SMCs, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularisation

Question 12

The classic and modern thrombogenic theory of atherosclerosis

Answer 12

• Classic: Micro-injuries in intima -> platelet adhesion -> vasoactive substances (serotonin, histamine) promote lipid infiltration
• Modern: TXA2/PGI2 increase, omega3 FA, low dose of aspirin

Question 13

Mesenchymal theory of atherosclerosis

Answer 13

• Matrix remodeling -> promotes deposition of lipids (inc. collagen, dec. elastic fibers + inc. matrix mass)

Question 14

Monoclonal theory of atherosclerosis

Answer 14

• Atherosclerotic lesions are benign SM tumors
• Normal arterial wall contains cells expressing the A and B allele of glucose-6-P dehydrogenase
• Most plaques are monotypic (containing only A or B allele)

Question 15

Inflammation theory

Answer 15

6 pathogens selected because they produce either a persistent infection or a persistent Ab response in host.
- Cytomegalovirus (CMV), Herpes simplex virus type 1 and 2 (HSV1/2), Hepatitis A (HAV), chlamydia pneumoniae, helicobacter pylori

Question 16

Possible causes of endothelial dysfunction (5)

Answer 16

1. Elevated and modiefied LDL (ox-LDL, small-LDL)
2. Genetic alteration
3. Elevated plasma homocysteine concentration
4. Infectious microorganisms (Herpes virus, chlamydia pneumoniae)
5. Combinations of these or other factors

Question 17

Effects of homocysteine (4)

Answer 17

Endothelial injury, prothrombotic, increases synthesis of collagen, free NO decreases