CD143 in the development of atherosclerosis

The expression of CD143 (angiotensin-I-converting enzyme, ACE) in cardiovas cular diseases may be an important determinant of local angiotensin and kin in concentrations. Much of the experimental and clinical evidence suggests a crucial role for Ang II in fibrogenesis and the development of atheroscle rosis. Therefore, we have studied the distribution of CD143 in atherosclero tic and non-atherosclerotic segments isolated from different parts of the h uman vascular tree, including aorta and coronary, carotid, brachial, renal, iliac and femoral arteries, and staged according to the AHA. Two hundred a nd thirty native and formalin-fixed specimens of 80 patients were analysed by sensitive APAAP-technique using ten different monoclonal and polyclonal antibodies to human CD143 and several controls. In non-atherosclerotic segm ents or intimal thickening, CD143 was found almost restricted to the endoth elial cells of adventitial arterioles and small muscular arteries. In contr ast, a striking accumulation of CD143 was detected in all early and advance d atherosclerotic lesions. This de-novo occurrence of CD143 within the inti mal vascular wall was caused by spindle-shaped subendothelial cells with ma crophagic/histocytic features, activated macrophages and foam cells. In add ition, advanced lesions of atherosclerosis showed a marked neo-expression o f CD143 in newly formed intimal microvessels. Hypocellular fibrotic plaques depleted in microvessels and macrophages showed only little CD143. The de- novo occurrence of CD143 was dependent on the stage of atherosclerosis but not on its particular localisation within the vascular system. This early a nd obligatory CD143 expression at an unusual vascular site may contribute t o unusual tissue levels of angiotensins as indicated by co-localisation of immunoreactive Ang II. Thus, it may be an important pathogenetic step in th e development of atherosclerosis and an established target for pharmacologi cal prevention. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.