Molecular mechanism of atherosclerosis plaque formation:

Accumulation of macrophage white blood cells in the walls of arteries which is promoted by low-density lipoproteins

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Inadequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL)

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Artery wall thickens as the result of a build-up of fatty materials such as cholesterol

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Formation of multiple plaques within the arteries

The atheromatous plaque is divided into three distinct components:

1. The atheroma, which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery

2. Underlying areas of cholesterol crystals

3. Calcification at the outer base of older or more advanced lesions.

   
   

Molecular mechanism of atherosclerosis:

Atherogenesis is a decades-long process in which the lumen of a blood vessel becomes narrowed by cellular and extracellular substances to the point of obstruction.

Stages of atherosclerotic plaque development:

Figure: Stages of atherosclerotic plaque development

A. The fatty streak is the earliest identifiable morphological change. 

This may be – 

1. pre-dated by endothelial dysfunction, 

2. detected using methods assessing vascular function (rather than morphology), and 

3. persist or deteriorate as the atherosclerotic process advances. 

B. The fatty streak is followed by the formation of an established plaque 

It is characterized by - 

-the accumulation of increasing numbers of macrophage foam cells and 

-a local chronic inflammatory infiltrate. 

C. The complicated plaque is characterized by – 

-smooth muscle cell migration and the formation of a fibrous cap, 

-the formation of a necrotic lipid core and 
-an ever-increasing inflammatory infiltrate. 

D. Plaque rupture

Plaque rupture may occur after the fibrous cap has been weakened by the production of degradative enzymes and reactive oxygen species by the inflammatory cellular infiltrate. 

This exposes highly prothrombotic material, which leads to the formation of thrombus that may result in the clinically recognized acute coronary syndromes.