The Pathophysiology of Atherosclerosis

By: VSS

Definition of Atherosclerosis

Atherosclerosis can be described as the hardening and narrowing of the arteries that occur due to a build up of atherosclerotic plaque in the arterial wall. This plaque usually contains white blood cells, smooth muscle cells, cholesterol, lipids, calcium, collagen and fibrin and over time increases in size.

The plaque eventually encroaches on the lumen of these vessels

How is an atherosclerotic plaque

formed?

The tissue layers of an artery

How are plaques formed?

An initial injury or dysfunction of the vascular endothelium is believed to trigger plaque formation or atherogenesis

Injury could be caused by Elevated levels of cholesterol and triglycerides in the

blood High blood pressure Cigarette smoking

Injury causes increased permeability of the endothelium to low density lipoproteins (LDLs)

How plaques are formed

LDLs penetrate endothelium and deposit in the arterial intima where they become oxidized by reactive oxygen species released by the dysfunctional endothelial cells

Oxidized LDLs activate endothelial cells to produce adhesion molecules

How plaques are formed The adhesion molecules bind

to leukocytes namely, monocytes and T-helper cells.

Once bound to the adhesion molecules, the leukocytes enter the intima where the monocytes differentiate into macrophages.

The macrophages take up oxidized LDLs and become “foam cells” which form a fatty streak in the artery wall.

How plaques are formed

The foam cells release chemokines to attract more macrophages

They also release IGF-1 which promotes Smooth muscle cell (SMC) migration from the tunica media into the intima, and their subsequent proliferation

The increased proliferation of SMC cells leads to increased synthesis of collagen which causes hardening of the plaque

How plaques are formed

T-Helper cells produce IFNγ which activate endothelial cells to produce more adhesion molecules and bind more white blood cells to produce even more foam cells

How plaques are formed When foam cells die, they

release their lipid contents into the plaque which drives the growth of the plaque

Foam cells also release proinflammatory cytokines and reactive oxygen species which both increase inflammation in the area

Pressure increases in the plaque which can cause the plaque to rupture and lead to thrombus formation

Thrombus formation

If the plaque ruptures, coagulation occurs to prevent the plaque from spilling its contents into the lumen of the vessel

The thrombus formed can impede blood flow leading to ischemia

Summary

References

https://www.youtube.com/watch?v=R6QTiBfzULE

Clinical Medicine – Kumar and Clarke