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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 项目4：肥胖症的血小板激活促进动脉瘤血栓性血管事件 Zhenyu li 肥胖与心血管死亡的风险增加有关，而不是其其他公认的后果，例如高血压和高脂血症。心血管死亡中这种过量的一个潜在因素可能与脂肪质量增加引起的促血管和促炎状态有关，脂肪质量的增加是动脉粥样硬化临床表现的发病机理的关键成分。血小板在动脉血栓形成中起着核心作用，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症心血管后果的必不可少的介体。与此相一致，肥胖与血小板聚集的增加，血小板激活标记（如P-选择素）的表面表达以及血小板微粒形成升高有关。更重要的是，脂肪质量的减少会导致血小板激活增强的标志物的归一化。但是，如何在肥胖症中激活血小板，以及与肥胖相关心血管疾病中血小板过度激活的因果作用。血小板的几种特征和经过验证的生物学活动使它们成为触发和维持肥胖症炎症反应的吸引人候选人。 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.