title: Low thrombogenicity of calcified atherosclerotic plaques is associated with bone morphogenetic protein-2-dependent inhibition of tissue factor expression.
abstract: Morphology of atherosclerotic plaque is a major determinant of plaque thrombogenicity. Calcified atherosclerotic lesions are less prone to thrombosis and contain less tissue factor (TF) than lipid-rich plaques. Although bone morphogenetic protein (BMP)-2 is a known mediator of vascular calcification, the role of BMP-2 in the regulation of plaque thrombogenicity has not been established. We hypothesized that the expression of BMP-2 within highly calcified atherosclerotic plaques inhibits TF expression and reduces thrombogenicity of calcified lesions. In the present study, we measured levels of TF and BMP-2 in human calcified and lipid-rich carotid plaques and studied the effects of BMP-2 on TF expression in human monocytes in vitro. Quantitative immunohistochemical analysis of endarterectomy specimens for TF and BMP-2 revealed that calcified plaques contained nearly three-times less TF antigen than lipid-rich ones. In contrast, calcified plaques expressed two-times more BMP-2 antigen than lipid-rich lesions. BMP-2 markedly decreased protein expression and surface redistribution of TF in activated human monocytes in vitro. BMP-2-mediated inhibition of TF expression in monocytes/macrophages could contribute to reduced thrombogenicity of calcified atherosclerotic plaques.
authors: Hematological Research Group, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. elena.egorina@uit.no
authors: Elena M
authors: EM
authors: Egorina
authors: Mikhail A
authors: MA
authors: Sovershaev
authors: Vladimir Y
authors: VY
authors: Bogdanov
authors: Timofey A
authors: TA
authors: Sovershaev
authors: John T
authors: JT
authors: Fallon
authors: Natalia
authors: N
authors: Seredkina
authors: Bjarne
authors: B
authors: Østerud
authors: John-Bjarne
authors: JB
authors: Hansen
mesh_terms: D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications / Q000473:pathology; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004691:Endarterectomy; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D006651:Histocytochemistry; D006801:Humans; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000737:chemistry*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000097:blood* / Q000150:complications / Q000473:pathology; D061205:Vascular Calcification / Q000097:blood* / Q000150:complications / Q000473:pathology
chemical_list: D055396:Bone Morphogenetic Protein 2; D008055:Lipids; D008070:Lipopolysaccharides; D013925:Thromboplastin