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(Circulation Research. 2004;95:877.)
© 2004 American Heart Association, Inc.

Molecular Medicine

C-Reactive Protein Enhances LOX-1 Expression in Human Aortic Endothelial Cells

Relevance of LOX-1 to C-Reactive Protein–Induced Endothelial Dysfunction

Ling Li, Nadia Roumeliotis, Tatsuya Sawamura, Geneviève Renier

From Department of Biomedical Sciences (L.L.) and Medicine (N.R., G.R.), University of Montreal, Centre Hospitalier de l’Université de Montréal (CHUM) Research Centre, Notre-Dame Hospital, Montreal, Quebec, Canada; and the Department of Bioscience (T.S.), National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka, Japan.

Correspondence to Dr Geneviève Renier, CHUM Research Centre, Notre-Dame Hospital, J-A De Seve Pavilion, Door Y 3622, 1560 Sherbrooke St East, Montreal, Quebec H2L 4M1, Canada. E-mail genevieve.renier{at}umontreal.ca

C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful predictor of cardiovascular events. Recent data suggest that CRP may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endothelial receptor for oxLDL that plays a pivotal role in oxLDL-induced endothelial dysfunction. Whether CRP may regulate endothelial LOX-1 and induce endothelial dysfunction through this receptor is unknown. In the present study, we studied the in vitro effect of CRP on LOX-1 expression in human aortic endothelial cells (HAECs) and the role of LOX-1 in CRP-induced human monocyte adhesion to endothelium and oxLDL uptake by endothelial cells. Incubation of HAECs with CRP enhanced, in a dose- and time-dependent manner, LOX-1 mRNA and protein levels. Induction of LOX-1 protein was already present at 5 µg/mL CRP and reached a maximum at 25 µg/mL. This effect was reduced by antibodies against CD32/CD64, endothelin-1 (ET-1) and interleukin-6 (IL-6). The extent of stimulation of LOX-1 achieved by CRP was comparable to that elicited by high glucose and IL-6 and remained unchanged in presence of these factors. Finally, CRP increased, through LOX-1, both human monocyte adhesion to endothelial cells and oxLDL uptake by these cells. We conclude that CRP enhances endothelial LOX-1 expression and propose a new mechanism by which CRP may promote endothelial dysfunction, that of inducing LOX-1.

Key Words: C-reactive protein • endothelium • lectin-like oxidized low-density lipoprotein receptor-1 • inflammation

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