C-reactive protein promotes platelet adhesion to endothelial cells: a potential pathway in atherothrombosis.
C-reactive protein (CRP) is a strong predictor for acute cardiovascular events. Several endothelial prothrombotic effects of CRP have been recently reported. This study examined the effect of CRP on bovine aortic endothelial cell (EC) activation and capacity to recruit human platelets under flow conditions using the cone and plate(let) analyser method. Human recombinant CRP promoted platelet adhesion in a dose- and time-dependent manner, with a maximal effect at 20 microg/ml (increase of 174% over baseline, P < 0.01). Similar effects were observed following incubation of EC with sera of transgenic mice that express human CRP (10 microg/ml). Anti-intercellular adhesion molecule-1 neutralising monoclonal antibody and nitric oxide donor, sodium nitroprusside, blocked the effect of CRP, reducing adhesion from 202% to 128% (P < 0.05) and 114% (P = 0.02) respectively. The pro-adhesive effect of CRP was abolished by calphostin C (a protein kinase C inhibitor), whereas the extracellular signal-regulated kinase antagonist, PD98059, did not have any effect. CRP promoted P-selectin expression on the EC surface and blockade of P-selectin reversed CRP-induced platelet adhesion. In conclusion, CRP promoted platelet adhesion to EC. Our results emphasise the possible role of CRP in linking inflammation and thrombosis and provide a potential mechanism for the high incidence of vascular events associated with high CRP levels.
Yaron
Gil
G
Department of Haematology, Hadassah Hebrew University Medical Centre, Jerusalem, Israel.
Brill
Alexander
A
Dashevsky
Olga
O
Yosef-Levi
Irit Mor
IM
Grad
Etty
E
Danenberg
Haim D
HD
Varon
David
D
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D050197:Atherosclerosis / Q000473:pathology*; D002097:C-Reactive Protein / Q000235:genetics / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D000077542:Eptifibatide; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D019007:P-Selectin / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D020030:Nitric Oxide Donors; D019007:P-Selectin; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D009599:Nitroprusside; D002097:C-Reactive Protein; D000077542:Eptifibatide