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首页 » 冠心病 » Nat Med:研究揭示为何黑人冠心病患者存活率低于白人

Nat Med:研究揭示为何黑人冠心病患者存活率低于白人

来源:中国科学报 2013-12-27 15:41

据《自然—医学》上的一项研究显示,与白人相比,黑人血液中血小板更容易被激活。由于血小板的激活会导致血液过度凝结,这项研究或有助于解释为何相比白人,冠心病黑人患者存活率较低。

Paul Bray等人对比了包括黑人和白人在内的154位健康人的血小板,发现黑人体内的血小板中的名为miR-376c的microRNA水平浓度低,这反过来导致其目标蛋白质数量较多。这种蛋白质又正好是凝血酶完全激活血小板所必需的。

这项发现突出了一个观点:在临床使用抗血栓类药物尤其是那些抑制凝血酶活性的药物时,要将种族差异因素考虑在内。(生物谷Bioon.com)

生物谷推荐的英文摘要

Nature Medicine           doi:10.1038/nm.3385

Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c

Leonard C Edelstein,  Lukas M Simon,  Raúl Teruel Montoya,  Michael Holinstat,  Edward S Chen,  Angela Bergeron,  Xianguo Kong,  Srikanth Nagalla,  Narla Mohandas,  David E Cohen, Jing-fei Dong,  Chad Shaw  & Paul F Bray

Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and PAR4 reactivity and were inversely correlated with PCTP mRNA levels, PC-TP protein levels and PAR4 reactivity. miR-376c regulated the expression of PC-TP in human megakaryocytes. A disproportionately high number of microRNAs that were differentially expressed by race and PAR4 reactivity, including miR-376c, are encoded in the DLK1-DIO3 locus and were expressed at lower levels in platelets from black subjects. These results suggest that PC-TP contributes to the racial difference in PAR4-mediated platelet activation, indicate a genomic contribution to platelet function that differs by race and emphasize a need to consider the effects of race when developing anti-thrombotic drugs.

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