Q. Describe the Basic Mechanisms in Plaque Formation?
In experimental models and human disease, the first morphologic phenomenon observed in plaque formation is adhesion of monocytes to an intact endothelial surface. This adhesion is followed by monocyte migration into the intima. In the intima, monocytes are activated, converted to macrophages, and may divide. Lipid uptake by macrophages then leads to the formation of the foam cell. Many factors act in concert to cause monocyte migration to allow the incoming monocytes to establish themselves in the intima. The endothelial surface is intact in the initial phase of coronary atherosclerosis. There is no exposure of the subendothelial connective tissue matrix and therefore no adhesion of platelets to the vessel wall. Much of the cholesterol and esters in a lipid core is released from the cytoplasm of dying foam cells. Active plaques contain numerous macrophages clustered at the edge of the core with the expression of a range of metalloproteinases that likely are engaged in the active destruction of the collagen matrix.
Smooth muscle cell migration and proliferation as well as collagen deposition are driven by growth factors produced by virtually every cell type, including smooth muscle cells themselves. The normal media is a vascular, but once intimal thickening occurs, new vessels grow in from the adventitia and reach the base of the plaque.