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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 子项目4说明 肥胖与心血管死亡风险增加有关。肥胖相关心血管死亡的一个潜在因素可能与脂肪量增加引起的促血栓和促炎症状态有关，这两者都是发病机制的关键组成部分。血小板在动脉血栓形成中发挥核心作用，在炎症状态下被激活，并受到特定脂肪因子的直接影响，因此有可能作为心血管后果的重要介质。 α-颗粒对于正常的血小板活性至关重要，许多炎症因子和细胞因子储存在 ¿ - 活化的而非静息的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，活化的血小板会释放转化生长因子-β (TGF-β)。 α-颗粒并已被证明可以增强脂肪组织中 1 型纤溶酶原激活剂抑制剂 (PAI-1) 的释放，因此，血小板分泌可能发挥作用。 cGMP/PKG 通路在饮食引起的肥胖的促炎症和促血栓形成中发挥着重要作用。此外，我们最近还发现了 Src 家族激酶，尤其是 Lyn 激酶的作用。因此，我们将操纵这些信号通路来确定血小板分泌在肥胖相关的促炎症和促血栓状态中的作用。