Recent models of atherogenesis have been based, in part, on the “response-to-injury” hypothesis proposed by Ross and colleagues [Ross, R. Nature. 1993;362:801]. The concept is that atherosclerosis begins as a response to chronic minimal injury to the endothelium (the continuous monolayer of cells lining the arterial wall) and that interactions among monocytes, lipoproteins, platelets, lymphocytes, and smooth muscle cells abet and continue the pathogenic process.
The main “battleground” of the atherosclerotic process in the intima, which lies just below the endothelium [Hajjar DP, Nicholson AC. American Scientist. 1995;83:460]. While the media (middle layer) appears to play some role — and perhaps the adventitia (outer layer) as well — the development of atherosclerosis is primarily characterized by an accumulation of complex lipids, proteins, and carbohydrates, as well as a proliferation of cells, in the intimal layer of an artery.
Ip and colleagues have proposed a pathophysiologic classification of vascular injury into three types [Ip JH, et al, 1990. Ip JH, et al, 1994].
Type I injury, a chronic minimal injury characterized by functional alterations of endothelial cells without significant morphologic changes (i.e., epithelial denudation), is thought to be caused primarily by the turbulence of blood flow. However, other factors appear to potentiate endothelial injury, including hypertension, hypercholesterolemia, circulating vasoactive amines, immunocomplexes, viral infections, and a chemical irritant in tobacco smoke.
Type II injury is characterized by denuding of the endothelium and superficial intimal injury. These changes, which appear to be the result of toxic products released by accumulating macrophages in the intima, are accompanied by platelet deposition with or without thrombus formation. Repetitive Type II injury of soft plaques, with thrombus incorporation, is thought to be a major mechanism for the progression of atherosclerosis.
Type III injury is typified by deep intimal and medial damage, accompanied by marked platelet aggregation and mural thrombosis. Vascular injury of this magnitude is seen following plaque rupture.
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