PLATELET ACTIVATION WITH OBESITY PROMOTES ATHEROTHROMBOTIC VASCULAR EVENTS

肥胖引起的血小板激活促进动脉粥样硬化性血管事件

• 批准号: 8174559
• 负责人: ZHENYU Li
• 金额: $ 24.02万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174559
• 关键词: Adipose tissue; Atherosclerosis; Biological; Blood Platelets; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Clinic; Computer Retrieval of Information on Scientific Projects Database; Environment; Event; Feedback; Funding; Grant; Hyperlipidemia; Hypertension; Inflammatory; Inflammatory Response; Institution; Mediator of activation protein; Obesity; P-Selectin; Pathogenesis; Platelet Activation; Platelet aggregation; Play; Research; Research Personnel; Resources; Role; Secondary to; Source; Surface; Testing; Thrombosis; United States National Institutes of Health; Vascular Endothelium; adipokines; cardiovascular risk factor

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 项目4：肥胖引起的血小板活化促进动脉粥样硬化血栓形成血管事件 李振宇 肥胖与心血管死亡风险增加相关，与其他公认的后果如高血压和高脂血症无关。导致心血管死亡的一个潜在因素可能与脂肪量增加诱导的促血栓形成和促炎症状态有关，这两者都是动脉粥样硬化临床表现发病机制的关键组成部分。血小板在动脉血栓形成中起核心作用，在炎症状态下被激活，并直接受到特定脂肪因子的影响，因此有可能作为肥胖心血管后果的重要介质。与此一致，肥胖与血小板聚集增加、血小板活化标志物如P-选择素的表面表达升高和血小板微粒形成增加有关。更重要的是，脂肪量的减少导致血小板活化增强标志物的正常化。然而，血小板在肥胖症中是如何被激活的，以及血小板过度激活在肥胖症相关的心血管疾病中的因果关系仍有待确定。血小板的几个特性和已证实的生物活性使其成为引发和维持肥胖炎症反应的有吸引力的候选者。本研究将检验中心假设，即继发于肥胖的血小板活化/分泌在触发和维持肥胖的促炎和促血栓形成状态中起因果作用，形成涉及脂肪组织、活化血小板和血管内皮的反馈回路，最终形成有利于动脉粥样硬化血栓形成血管事件的环境。