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: 8360249
• 负责人: ZHENYU Li
• 金额: $ 23.84万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360249
• 关键词: Adipose tissue; Alpha Granule; Atherosclerosis; Blood Platelets; Blood Vessels; CCL2 gene; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Clinic; Cyclic GMP; Cytoplasmic Granules; Diet; Endothelial Cells; Event; Family; Funding; Grant; Inflammatory; Mediator of activation protein; Monocyte Chemoattractant Proteins; National Center for Research Resources; Obesity; Pathogenesis; Pathway interactions; Phosphotransferases; Plasminogen Activator Inhibitor 1; Platelet Activation; Play; Principal Investigator; Property; Research; Research Infrastructure; Resources; Rest; Role; Signal Pathway; Source; Thrombosis; Transforming Growth Factor beta; United States National Institutes of Health; adipokines; cardiovascular risk factor; cost; cytokine

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Sub-project 4 description Obesity is associated with an increased risk of cardiovascular death. One potential contributing factor in obesity-associated 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. alpha-Granules are essential to normal platelet activity. Many inflammatory factors and cytokines are stored in ¿-Granules. Activated, but not resting platelets are able to alter the chemotactic properties of endothelial cells by inducing the secretion of monocyte chemoattractant protein (MCP-1). Similarly, transforming growth factor-beta (TGF-beta) is released from activated platelet alpha-granules and has been shown to augment the release of type-1 plasminogen activator inhibitor (PAI-1) from adipose tissue. Therefore, platelet secretion may play an important role in the pro-inflammatory and pro-thrombotic consequences of diet-induced obesity. The cGMP/PKG pathway plays a critical role in platelet secretion. In addition, we have recently identified a role for Src family kinses, especially the Lyn kinase, in platelet secretion. Therefore, we will manipulate these signaling pathways to identify a role of platelet secretion in obesity-associated pro-inflammatory and pro-thrombotic states.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 子项目4说明 肥胖与心血管死亡风险增加有关。肥胖相关性心血管死亡的一个潜在促成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重要组成部分。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。α-颗粒对正常血小板活性至关重要。许多炎症因子和细胞因子储存在颗粒中。活化而非静息血小板能够通过诱导单核细胞趋化蛋白（MCP-1）的分泌来改变内皮细胞的趋化特性。类似地，转化生长因子-β（TGF-β）从活化的血小板α-颗粒释放，并且已显示增加1型纤溶酶原激活物抑制剂（派-1）从脂肪组织的释放。因此，血小板分泌可能在饮食诱导的肥胖的促炎和促血栓形成后果中起重要作用。cGMP/PKG通路在血小板分泌中起关键作用。此外，我们最近发现Src家族激酶，特别是林恩激酶，在血小板分泌中的作用。因此，我们将操纵这些信号通路，以确定血小板分泌在肥胖相关的促炎症和促血栓形成状态中的作用。