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C-reactive protein enhances LOX-1 expression in human aortic endothelial cells: relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction.
- Source :
-
Circulation research [Circ Res] 2004 Oct 29; Vol. 95 (9), pp. 877-83. Date of Electronic Publication: 2004 Oct 07. - Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- Anti-Infective Agents pharmacology
Aorta cytology
C-Reactive Protein physiology
Cells, Cultured cytology
Cells, Cultured drug effects
E-Selectin analysis
Endothelial Cells cytology
Endothelial Cells drug effects
Endothelial Cells metabolism
Endothelium, Vascular cytology
Endothelium, Vascular metabolism
Gene Expression Regulation drug effects
Glucose pharmacology
Humans
Inflammation metabolism
Intercellular Adhesion Molecule-1 analysis
Interleukin-6 pharmacology
Lipopolysaccharides pharmacology
NF-kappa B antagonists & inhibitors
Nitriles
RNA, Messenger biosynthesis
Receptors, LDL genetics
Receptors, LDL physiology
Receptors, Oxidized LDL
Scavenger Receptors, Class E
Sulfones
Vascular Cell Adhesion Molecule-1 analysis
C-Reactive Protein pharmacology
Cell Adhesion drug effects
Endothelium, Vascular drug effects
Leukocytes, Mononuclear drug effects
Lipoproteins, LDL metabolism
Receptors, LDL biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 95
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 15472120
- Full Text :
- https://doi.org/10.1161/01.RES.0000147309.54227.42