Adhesion molecules influencing atherosclerosis.
Life limiting diabetes heart problems predominantly result from accelerated thrombogenesis superimposed on a localized arterial vessel stenosis (atherothrombosis). The atherosclerotic process is a slowly progressing vitious cycle of self-amplifying cell-cell interactions. Initially, corpuscular blood elements, predominantly monocytes adhere to locally activated endothelial cells, before they convert into lipid laden macrophages. The proliferative response of media smooth muscle cells to foam cell derived mediators proceeds to the fibrous plaque where underlying subendothelial matrix material activates bypassing platelets. The new concept of adhesion molecules explains how streaming white blood cells can locally adhere to the endothelial cells (selectin mediated), become triggered, stick (integrin mediated) and consecutively transmigrate. P-Selectin rapidly appears in the outer membrane of activated endothelial cells and platelets. It serves as receptor for sialic acid containing oligosaccharides within the monocyte/PMN membrane. These cells adhere to locally activated endothelium (nondenuding injury) and form nidus for the further adherence of activated platelets. Later, when platelets become activated in response to nuding endothelial injury, exposure of P-Selectin leads to the parallel local recruitment of white blood cells. Diabetic patients with clinically overt angiopathy, but also immediately after onset of the metabolic disease, were shown to have increased levels of circulating P-Selectin positive platelets. Therefore, it is suggested that enhanced platelet-leukocyte interaction might be pathogenetic for atherogenesis from the very beginning as it must be considered of importance for reperfusion injury and remodelling in a highly affected myocardium when the catastrophe of myocardial infarction has finally occurred.
Tschoepe
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Diabetes Research Institute, Heinrich Heine University, Düsseldorf, Germany. tschoepe@dfi.uni-duesseldorf.ole
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001792:Blood Platelets / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003925:Diabetic Angiopathies / Q000097:blood; D006801:Humans; D019007:P-Selectin / Q000097:blood / Q000502:physiology
D015815:Cell Adhesion Molecules; D019007:P-Selectin