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C‐reactive protein promotes platelet adhesion to endothelial cells: a potential pathway in atherothrombosis
Author(s) -
Yaron Gil,
Brill Alexander,
Dashevsky Olga,
YosefLevi Irit Mor,
Grad Etty,
Danenberg Haim D.,
Varon David
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06198.x
Subject(s) - platelet , c reactive protein , platelet activation , inflammation , sodium nitroprusside , chemistry , p selectin , adhesion , pharmacology , medicine , nitric oxide , organic chemistry
Summary 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 μ g/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 μ g/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.