C-reactive protein promotes platelet adhesion to endothelial cells: a potential pathway in atherothrombosis

被引:55
作者
Yaron, Gil
Brill, Alexander
Dashevsky, Olga
Yosef-Levi, Irit Mor
Grad, Etty
Danenberg, Haim D. [1 ]
Varon, David
机构
[1] Hadassah Hebrew Univ, Med Ctr, Heart Inst, Jerusalem, Israel
[2] Hadassah Hebrew Univ, Med Ctr, Dept Haematol, Jerusalem, Israel
[3] Hadassah Hebrew Univ, Med Ctr, Dept Cardiol, Jerusalem, Israel
[4] Hadassah Hebrew Univ, Med Ctr, Dept Internal Med, Jerusalem, Israel
关键词
C-reactive protein; platelets; endothelium; adhesion; cone and platelet analyser;
D O I
10.1111/j.1365-2141.2006.06198.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu 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 mu 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.
引用
收藏
页码:426 / 431
页数:6
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