Atherosclerosis

Question 1

What are the components of an atherosclerotic layer

Answer 1

1. Fibrous cap- dynamic equilibrium of smooth muscle and collagen
2. Cellular layer- smooth muscle, lymophocytes, macrophages and less connective tissue

Lipid core - cholesterol clefts, lipids and foam cells

Question 2

Pathophysiology of atherosclerosis

Answer 2

. Endothelial cell damage causes increased permeability of the endothelial cells, this allows for LDL to enter the tunica intima. The tunica intima is a well oxygenated area and there is the presence of ROS and the absence of NO which normally has vasodilatory effecrs, this causes LDL to be oxidised and form foam cells. The oxidation of LDL causes the recruitment of leukocytes (Monocytes and T cells). The oxidised LDL is recognised by the immune system as foreign, thus monocytes differentiate into macrophages and engulf the oxidised LDL. Macrophages continue to do this until they undergo apopotosis or necrosis, which forms the basis of the lipid rich core

Moreover, the Monocytes recruit chemokines and cytokines which further produce ROS leading to further oxidised LDL formation and the consequent further recruitment of monocytes and t cells, suggesting that atherosclerosis is a chronic inflammatory process. Furthermore, cytokines cause smooth muscle cell migration and aggregation from the tunica media to the tunica intima and express synthetic and elastic properties that they do not exhibit in the tunica media, this smooth muscles secerete extracellular matrix such as collagen which stabilises the lipid core.
Thus, the fibroproliferative activity of the smooth muscle and accumulating lipid rich cores resulting in the formation of a atherosclerosis.

Question 3

What increases the risk of Atherosclerosis and what complications can atherosclerosis lead to

Answer 3

Risk:
-Increased age
- high bp
- hyperlipedemia
- Hypertension
-smoking and drugs- increased ROS

Complications:
- myocardial infarction
- Stroke
- Peripheral vascular disease

Question 4

Normal endothelial cell function

Answer 4

1. Antiinflammatory: prevents the leukocyte adhesion and migration
2. Antithrombotic: prevents platelet recruitemnt adhesion and migration
3. Vascular tone- release of NO causes vasodilation

Question 5

what is endothelial cell damage triggered by

Answer 5

-High BP
-Inflammation stimulated by chemokines and cytokines
-turbulent blood flow

Question 6

endothelial activation results in

Answer 6

increased permeability
platelet aggregation
cytokine release
Contraction due to histamine release
Growth factor secretion– VEGF stimulates new blood vessel formation
PGDF- fibrosis

Question 7

endothelial damage results

Answer 7

expresses procoagulant molecules - release VWF binds to platlets

underlying basement membrane and collagen get exposed

release of growth factors -elastin and proteoglycans- smooth muscle cell migration