Oxidised and native low-density lipoproteins induce the release of von Willebrand factor from human endothelial cells in vitro.
Increased low-density lipoprotein (LDL)-cholesterol is a risk factor for atherosclerosis--a disease in which damage to the endothelium is believed to be an important early step. Increased levels of the endothelial marker von Willebrand factor (vWF) in the plasma of patients with hypercholesterolaemia and atherosclerosis probably reflect this process. In this study we seek to link the established observation that oxidised LDL-cholesterol is cytotoxic to human umbilical vein endothelial cells (HUVECs) in vitro with the common finding of raised plasma vWF in patients with atherosclerosis by incubating HUVECs with physiological/pathological levels of native and oxidised LDL-cholesterol for up to 48 h. Microphotography revealed morphological changes in the HUVECs within 24 h, becoming severe at 48 h, which was mirrored by increased levels of vWF (ELISA) and the release of preloaded radioactive (111)indium tracer into culture supernatants. Our data support and extend the hypothesis that oxidised LDL is directly cytotoxic to HUVECs, and, in addition, provide an important link between in vitro studies and clinical studies where endothelial cell markers such as vWF are increased in the plasma of patients with hypercholesterolaemia and atherosclerosis.
Blann
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Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK. a.blann@bham.ac.uk
Burrows
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G
McCollum
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D016923:Cell Death / Q000187:drug effects; D008078:Cholesterol, LDL / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000378:metabolism*
D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014841:von Willebrand Factor