Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, China.
Mol Med. 2012 Mar 27;18(1):159-66. doi: 10.2119/molmed.2011.00295.
The fundamental mechanisms that underlie platelet activation in atherothrombosis are still obscure. Oxidative stress is involved in central features of atherosclerosis. Platelet-derived microvesicles (PMVs) could be important mediators between oxidative stress and platelet activation. CD36 could be a receptor of PMVs, thus generating a PMV-CD36 complex. We aimed to investigate the detailed pathway by which oxidative damage contributes to platelet activation by the PMV-CD36 complex. We found that oxidized low-density lipoprotein stimulated the generation of PMVs. PMVs enhanced normal platelet activation, as assessed by the expression of integrin α(IIb)β₃, secretion of soluble P-selectin and platelet aggregation, but CD36-deficient platelets were not activated by PMVs. The function of the PMV-CD36 complex was mediated by the MKK4/JNK2 signaling axis. Meanwhile, PMVs increased the level of 8-iso-prostaglandin-F2α, a marker of oxidative stress, in a CD36- and phosphatidylserine-dependent manner. We concluded that PMVs are important mediators between oxidative stress and platelet activation. PMVs and CD36 may be effective targets for preventing platelet activation in cardiovascular diseases.
血小板在动脉血栓形成中激活的基本机制仍不清楚。氧化应激参与了动脉粥样硬化的核心特征。血小板衍生的微小囊泡（PMVs）可能是氧化应激和血小板激活之间的重要介质。CD36 可能是 PMVs 的受体，从而产生 PMV-CD36 复合物。我们旨在研究氧化损伤如何通过 PMV-CD36 复合物导致血小板激活的详细途径。我们发现氧化低密度脂蛋白刺激 PMVs 的产生。PMVs 增强了正常血小板的激活，如整合素 α(IIb)β₃的表达、可溶性 P-选择素的分泌和血小板聚集所评估的那样，但 PMVs 不能激活 CD36 缺陷型血小板。PMV-CD36 复合物的功能是由 MKK4/JNK2 信号轴介导的。同时，PMVs 以 CD36 和磷脂酰丝氨酸依赖的方式增加了氧化应激标志物 8-异前列腺素 F2α的水平。我们得出结论，PMVs 是氧化应激和血小板激活之间的重要介质。PMVs 和 CD36 可能是预防心血管疾病中血小板激活的有效靶点。
