C-Reactive Protein Isoforms Differ in Their Effects on Thrombus Growth
C-Reactive Protein Isoforms Differ in Their Effects on Thrombus Growth
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DOI：
10.1161/atvbaha.108.174359
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发表时间：
2008-12-01
影响因子：
8.7
通讯作者：
Badimon, Lina
中科院分区：
文献类型：
--
作者：
Molins, Blanca;Pena, Esther;Badimon, Lina
目的-我们研究的影响，自然（natCRP）和修改CRP（mCRP）亚型对血小板粘附和血栓生长动脉flow.Methods和结果-血液灌注超过I型胶原在1500 s（-1）的壁剪切速率，血小板沉积和血栓生长进行了评估，通过共聚焦显微镜。在灌注实验之前将natCRP和mCRP与血液一起孵育，或者将其固定在胶原表面中并暴露于流动的血液。当直接与血液孵育时和固定在胶原表面时，mCRP显著增加血小板粘附和血栓生长（P < 0.05）。相比之下，natCRP没有发挥任何作用。共聚焦免疫组化显示粘附血小板表面和血栓内存在CRP，并显示与mCRP孵育的流出血小板中P-选择素和CD 36上调（P < 0.05）。激动剂诱导的血小板活化的流式细胞术分析表明，mCRP，而不是natCRP，显著增加血小板表面P-选择素（P < 0.05），而不改变CD 63和PAC-1。结论-我们的数据表明，虽然血清natCRP可能不影响血栓生长，mCRP显示血栓形成前的表型，不仅增加血小板沉积，而且在动脉血流条件下血栓生长。（Arterioscler Thromb Vasc Biol.2008; 28：2239-2246.）
Objective - We studied the impact of native (natCRP) and modified CRP (mCRP) isoforms on platelet adhesion and thrombus growth under arterial flow.Methods and Results - Blood was perfused over type I collagen at a wall shear rate of 1500 s(-1), and platelet deposition and thrombus growth were evaluated by confocal microscopy. natCRP and mCRP were either incubated with blood before perfusion experiments or immobilized in the collagen surface and exposed to flowing blood. mCRP significantly increased platelet adhesion and thrombus growth when directly incubated with blood and when immobilized on a collagen surface (P < 0.05). In contrast, natCRP did not exert any effect. Confocal immunohistochemistry revealed the presence of CRP on the surface of adhered platelets and within the thrombus and showed an upregulation of P-selectin and CD36 in effluent platelets preincubated with mCRP (P < 0.05). Flow cytometry analysis of agonist-induced platelet activation demonstrated that mCRP, but not natCRP, significantly increased platelet surface P-selectin (P < 0.05) without modifying CD63 and PAC-1.Conclusions - Our data indicate that whereas serum natCRP may not affect thrombus growth, mCRP displays a prothrombotic phenotype enhancing not only platelet deposition, but also thrombus growth under arterial flow conditions. (Arterioscler Thromb Vasc Biol. 2008; 28: 2239-2246.)