The endothelium in atherogenesis.
The focus of this article is an overview of the endothelial changes that initiate and perpetuate the process of atherogenesis. The endothelium can undergo a series of changes which allow it to participate in the inflammatory response; this is known as endothelial cell activation (ECA). The five core changes of ECA are loss of vascular integrity; expression of leucocyte adhesion molecules; change in phenotype from antithrombotic to prothrombotic; cytokine production, and upregulation of HLA molecules. The diverse effects of ECA share a common intracellular control mechanism through the activation of the transcription factors including Nuclear Factor kappaB. ECA is an initiating step in atherogenesis. Modified low density lipoproteins are probably the major cause of endothelial cell activation in atherogenesis, and become especially so after oxidation, glycation (in diabetes) or incorporation in immune complexes. In antiphospholipid syndrome (APS), antiendothelial cell antibodies have been detected in up to 67% of patients. In vitro studies suggest that aPL causes ECA and thus lead to speculation that aPL by causing ECA may initiate atherogenesis. Further clinical and in vitro studies are required to address these issues.
Hunt
B J
BJ
Department of Haematology, Guy's and St Thomas' Trust, London, UK. Beverley.Hunt@gstt.sthames.nhs.uk
D016736:Antiphospholipid Syndrome / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic
D015815:Cell Adhesion Molecules; D016207:Cytokines; D006680:HLA Antigens; D008077:Lipoproteins, LDL