The Pathogenesis of the Atherosclerotic Plaque

The Pathogenesis of the Atherosclerotic Plaque

Atherosclerosis is the main cause of coronary artery disease. The process begins as disruption of endothelial function due to the accumulation of lipoprotein droplets in the intima of the coronary vessels. Water insoluble lipids are carried in the bloodstream attached to water soluble apolipoproteins (lipoproteins). High concentrations of low density lipoprotein (LDL) can permeate an already disrupted or dysfunctional endothelium where it undergoes oxidation and, in diabetics, glycation. Modified LDL attracts leukocytes into the intima and can be scavenged by macrophages leading to the formation of foam cells. These cells replicate giving rise to one of the earliest pathological lesions; the fatty streak. The fatty streak is the earliest visualized lesion of atherosclerosis.

Smooth muscle cells are then recruited and migrate to the site of the foamy cells. Smooth muscle cells proliferate and manufacture extracellular matrix. A large volume of the plaque is occupied by extracellular matrix (collagen and proteoglycan) secreted by the smooth muscle cells. The fatty streak is now transformed into the fibrous plaque. At this point the lesion begins to encroach on the lumen of the vessel. Small blood vessels form in these plaques (angiogenesis) and these plaques can subsequently calcify. Inflammation plays an important role in promoting smooth muscle cell migration and proliferation. The final lesion, the advanced complicated lesion, consists of a fibrous cap overlying a lipid rich core which also contains necrotic material, this core is highly thrombogenic.