PLATELET ACTIVATION WITH OBESITY PROMOTES ATHEROTHROMBOTIC VASCULAR EVENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目4：肥胖患者的血小板活化促进动脉粥样硬化性血栓形成 李振宇 肥胖与心血管死亡风险的增加有关，独立于其其他公认的后果，如高血压和高脂血症。心血管死亡人数增加的一个潜在因素可能与脂肪质量增加引起的血栓前状态和炎症状态有关，这两种状态都是动脉粥样硬化临床表现发病的关键组成部分。血小板在动脉血栓形成中起中心作用，在炎症状态下被激活，并直接受到特定脂肪因子的影响，因此有可能成为肥胖导致的心血管后果的重要中介。与此一致的是，肥胖与血小板聚集性增加、P-选择素等血小板活化标志物表面表达增加以及血小板微粒形成增加有关。更重要的是，脂肪质量的减少会导致血小板活化增强的标志物正常化。然而，如何在肥胖中激活血小板，以及在肥胖相关的心血管疾病中血小板过度激活的因果作用仍有待确定。血小板的几个特性和已证实的生物活性使其成为触发和维持肥胖的炎症反应的吸引人的候选者。这项研究将检验中心假设，即肥胖继发的血小板激活/分泌在触发和维持肥胖的促炎和促血栓状态中起因果作用，创建一个涉及脂肪组织、激活的血小板和血管内皮细胞的反馈循环，最终在有利于动脉粥样硬化血栓形成的血管事件的环境中达到顶峰。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project 4: Platelet Activation with Obesity Promotes Atherothrombotic Vascular Events Zhenyu Li Obesity is associated with an increased risk of cardiovascular death independent of its other recognized consequences such as hypertension and hyperlipidemia. One potential contributing factor to this excess in cardiovascular deaths may be related to the pro-thrombotic and pro-inflammatory states induced by increases in adipose mass, both of which are critical components of the pathogenesis of the clinic manifestations of atherosclerosis. Platelets play a central role in arterial thrombosis, are activated in inflammatory states, and are directly influenced by specific adipokines, and therefore have the potential to serve as an essential mediator of the cardiovascular consequences of obesity. Consistent with this, obesity has been associated with increases in platelet aggregation, elevations in surface expression of markers of platelet activation such as P-selectin, and heightened platelet microparticle formation. More importantly, reduction in adipose mass leads to normalization of markers of enhanced platelet activation. However, how platelets are activated in obesity, and a causal role for platelet hyperactivation in obesity-related cardiovascular disorders remains to be established. Several characteristics and proven biological activities of platelets make them an appealing candidate for triggering and maintaining the inflammatory response of obesity. This study will test the central hypothesis that platelet activation/secretion secondary to obesity plays a causal role in triggering and maintaining the pro-inflammatory and pro-thrombotic state of obesity, creating a feedback loop involving adipose tissue, activated platelets and vascular endothelium that culminates in an environment favorable for atherothrombotic vascular events.