What is Atherosclerosis initiation by fibroblast plaque is mediated by injury to- and explain in detail?
Ans. is 'd' i.e., Endotheliumo The most acceptable hypothesis for the pathogenesis of atherosclerosis is "the response to injury hypothesis". o According to this hypothesis, atherosclerosis is a chronic inflammatory response of the aerial wall initiated by injury to endothelium.Pathogenesis of atherosclerosis Following stages occurs in the pathogenesis of Atherosclerosis1. Endothelial injuryo Earliest stages of the development of atherosclerosis are mediated by the inflammatory cascade.o Inflammation mediated injury to endothelium is the cornestone in the development of atherosclerosis.o After injury, endothelium is activated and there is increased expression of adhesion molecule-VCAM-1 andthere is increased permeability to endothelium.o TNF is the major cytokine to induce this expression.2. Migration of leukocyteso When VCAM- 1 is expressed on endothelium, leukocytes adhere to the endothelium.o Leukocytes than cross the endothelial barrier and begin to accumulate in subendothelial intimal space.o Macrophages engulf LDL cholesterol and form foam cells --> formation of earliest lesion, i.e. fatty streak.o Macrophages also form oxygen free radicals that cause oxidation of LDL to yield oxidized LDL (modifiedLDL).Smooth muscle cell migration and proliferationo Inflammatory cells in subendothelial intimal space secrete cytokines, mainly PDGF, TGF-a and FGF which cause migration of smooth muscle cells from media to subendothelial intimal space as well as their proliferation.4. Maturation of plagueo Smooth muscle cells synthesize extracellular matrix (especially collegen) and conve a fatty streak into a mature fibrofatty atheroma, and contribute to the progressive growth of atherosclerotic lesions.