Describe the pathophysiology of coronary atherosclerosis

- Abdominal aorta.

- Coronary artery.

- Popliteal artery.

- Carotid artery.

Most common arteries affected by atherosclerosis

- Left anterior descending artery.

- Right coronary artery.

- Left circumflex artery.

Most common sites of coronary atherosclerosis

- A raised lesion with a soft lipid core, covered by a fibrous cap.

What is an atheroma?

1. Atheroma starts to develop as a result of damage to endothelium.

2. Debris including cholesterol, fats and lipoproteins start to accumulate in the tunica intima.

3. High concentrations of LDL enter the endothelium and become oxidised.

4. The altered LDL then attracts monocytes to the site.

5. Monocytes enter endothelium and become macrophages where they engulf lipoproteins (which include mainly LDL). In this process they become FOAM cells (lipoproteins give them a foamy appearance.)

6. FOAM cells secrete more cytokines which attract more macrophages and a cycle is formed, a mound of FOAM cells form on the vessel wall.

7. These FOAM cells give rise to the earliest visible form of an atheroma called a fatty streak.

8. The fatty streak then attracts smooth muscles to the site, where they proliferate and secrete a matrix of collagen and proteoglycan (Which makes up a large portion of the plaque).

9. The fatty streak then become a fibrous plaque, which pushes on the inner wall of the blood vessel and decreases luminal space.

10. If endothelium covering the plaque gets damaged, this can lead to an accumulation of platelets onto the plaque and form a thrombus.

11. If thrombus breaks off and travels down stream it is called an embolus.

Describe step by step the pathogenesis of coronary atherosclerosis

- They increase local reactive oxygen species (ROS), which cause membrane and mitochondrial damage.

How does hypercholesterolaemia/hyperlipidemia cause endothelial disfunction?