title: Down-regulation of endothelial expression of endothelial cell protein C receptor and thrombomodulin in coronary atherosclerosis.
abstract: Coronary atherosclerosis with occlusive thrombosis is the major cause of acute myocardial infarction. Although plaque rupture is usually hypothesized to be the predisposing event in coronary thrombosis, the possibility cannot be excluded that local changes in the anticoagulant properties of the endothelium overlying the plaque contribute to this process. It is evident that thrombomodulin and the endothelial cell protein C receptor are critical players in the control of the thrombogenic process. This study examined whether thrombomodulin and the endothelial cell protein C receptor are down-regulated on endothelial cells overlying the atherosclerotic plaque in coronary arteries and thus could potentially favor local thrombus formation. Sections of archival left and right coronary arteries (n = 18 each) with severe atherosclerosis from the native heart of six patients who underwent heart transplantation were immunostained for CD31, CD34, endothelial cell protein C receptor, and thrombomodulin using a streptavidin-biotin-peroxidase method. Controls included left and right coronary arteries from autopsy cases with no atherosclerosis (n = 6), and also from cases with mild atherosclerosis (n = 5). The apparent density of all of these proteins was much higher in control than in atherosclerotic arteries. Our findings support the hypothesis that both endothelial cell protein C receptor and thrombomodulin are down-regulated in coronary arteries with atherosclerosis. These changes would be expected to result in reduced inhibition of thrombogenic and anti-inflammatory activity on the endothelium overlying atherosclerotic regions and thus could contribute to coronary thrombosis.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, the Howard Hughes Medical Institute and the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Laszik
authors.forename: X J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: G L
authors.initials: GL
authors.lastname: Ferrell
authors.forename: F G
authors.initials: FG
authors.lastname: Silva
authors.forename: C T
authors.initials: CT
authors.lastname: Esmon
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001779:Blood Coagulation Factors; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D001779:Blood Coagulation Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; C091963:activated protein C receptor