Published online before print October 7, 2004, doi: 10.1161/01.RES.0000147309.54227.42
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Submitted on March 31, 2004
Revised on August 24, 2004
Accepted on September 28, 2004
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 ;
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.
* To whom correspondence should be addressed. 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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