Hemodynamics and PKC Signaling in Atherosclerosis

动脉粥样硬化中的血流动力学和 PKC 信号传导

• 批准号: 6936943
• 负责人: RICHARD A MAGID
• 金额: $ 1.57万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936943
• 关键词: animal tissue; aorta; atherosclerosis; bioassay; biological signal transduction; confocal scanning microscopy; disease /disorder etiology; disease /disorder proneness /risk; enzyme activity; enzyme mechanism; gene expression; hemodynamics; isozymes; pathologic process; phosphorylation; postdoctoral investigator; protein kinase C; protein localization; protein protein interaction; proteomics; swine; vascular endothelium; western blottings

DESCRIPTION (provided by applicant): The objective of this proposal is to reveal how the local hemodynamic environment alters the function of protein kinase C in aortic endothelial cells. To study the steady-state in vivo, we will utilize protein from freshly isolated endothelial cells in regions of disturbed flow (inner aortic arch) and undisturbed flow (descending thoracic aorta) of normal adult pigs. The first aim will seek to identify the responsible isozymes and understand the mechanism behind our observation that PKC activity is increased in DF regions. The second aim will use proteomics to identify those proteins which interact with or are substrates for PKC. This information is critical for our attempts to understand the consequences of an focal increase in PKC activity. Thus, this project will provide novel information on the steady-state differences between athero-prone and athero-protected endothelial cells. This in turn has the potential to suggest novel pathways for anti-atherosclerotic interventions.

描述（由申请人提供）：本提案的目的是揭示局部血流动力学环境如何改变主动脉内皮细胞中蛋白激酶C的功能。为了研究体内稳态，我们将利用正常成年猪血流受干扰（内主动脉弓）和未受干扰血流（降胸主动脉）区域中新鲜分离的内皮细胞的蛋白质。第一个目标将寻求确定负责的同工酶并了解我们观察到 DF 区域 PKC 活性增加背后的机制。第二个目标是使用蛋白质组学来识别那些与 PKC 相互作用或作为 PKC 底物的蛋白质。这些信息对于我们尝试了解 PKC 活动集中增加的后果至关重要。因此，该项目将提供有关动脉粥样硬化倾向内皮细胞和动脉粥样硬化保护内皮细胞之间稳态差异的新信息。这反过来有可能提出抗动脉粥样硬化干预的新途径。