Leng Xing-Hong, Hong Song Yun, Larrucea Susana, Zhang Wei, Li Tong-Tong, López José A, Bray Paul F
Medicine/Thrombosis Research, Baylor College of Medicine, Houston, TX 77030, USA.
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):376-81. doi: 10.1161/01.ATV.0000110445.95304.91. Epub 2003 Dec 4.
It has been reported that women fare worse after ischemic coronary events, but the mechanisms remain unclear. Because platelets play a central role in the formation of occlusive thrombi at sites of ruptured atherosclerotic plaques, we studied male/female paired mouse littermates for sex differences in platelet function.
We compared platelet reactivity in male/female mouse littermates by monitoring agonist-induced fibrinogen (FGN) binding and platelet aggregation. Compared with the platelets from males, platelets from females bound more FGN in response to low concentrations of thrombin and collagen-related peptide. Female platelets also demonstrated greater aggregation in response to adenosine diphosphate and collagen-related peptide. Platelet protein tyrosine phosphorylation on activation also showed small differences between sexes. These differences are independent of platelet size and surface expression of alphaIIbbeta3 and GPIb-IX-V, and they were not blocked by apyrase or aspirin. The sex differences we observed were intrinsic to platelets, because they were observed in washed platelets, but not when platelets were in plasma.
The platelets of female mice were more reactive than those of males in a manner independent of COX-1 and secreted ADP.
据报道,女性在缺血性冠状动脉事件后情况更糟,但其机制仍不清楚。由于血小板在动脉粥样硬化斑块破裂部位闭塞性血栓的形成中起核心作用,我们研究了雄性/雌性配对的同窝小鼠血小板功能的性别差异。
我们通过监测激动剂诱导的纤维蛋白原(FGN)结合和血小板聚集来比较雄性/雌性同窝小鼠的血小板反应性。与雄性小鼠的血小板相比,雌性小鼠的血小板在低浓度凝血酶和胶原相关肽作用下结合更多的FGN。雌性血小板对二磷酸腺苷和胶原相关肽的反应也表现出更大的聚集。激活时血小板蛋白酪氨酸磷酸化在性别之间也存在微小差异。这些差异与血小板大小以及αIIbβ3和GPIb-IX-V的表面表达无关,并且不受腺苷三磷酸双磷酸酶或阿司匹林的阻断。我们观察到的性别差异是血小板固有的,因为在洗涤后的血小板中可以观察到,但血小板在血浆中时则不然。
雌性小鼠的血小板比雄性小鼠的血小板反应性更强,且这种方式独立于COX-1和分泌的ADP。