C-reactive protein enhances LOX-1 expression in human aortic endothelial cells: relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction.
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 microg/mL CRP and reached a maximum at 25 microg/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.
Department of Biomedical Sciences, University of Montreal, Centre Hospitalier de l'Université de Montréal Research Centre, Notre-Dame Hospital, Montreal, Quebec, Canada.
Ling
L
Li
Nadia
N
Roumeliotis
Tatsuya
T
Sawamura
Geneviève
G
Renier
D000890:Anti-Infective Agents / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002097:C-Reactive Protein / Q000494:pharmacology* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D019040:E-Selectin / Q000032:analysis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015850:Interleukin-6 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009570:Nitriles; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D013450:Sulfones; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D000890:Anti-Infective Agents; C416282:BAY 11-7085; D019040:E-Selectin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D009570:Nitriles; C495137:OLR1 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D013450:Sulfones; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D005947:Glucose