Effekte einer endothel-spezifischen PGC-1alpha Deletion auf die Modulation der Gefäßfunktion

内皮特异性 PGC-1α 缺失对血管功能调节的影响

• 批准号: 231703234
• 负责人: Dr. Swenja Kröller-Schön
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/231703234?language=en
• 关键词: Effekte; einer; endothel; spezifischen; PGC

The transkriptional coactivator PGC-1alpha plays a fundamental role in mitochondrial biogenesis and function. Data from our own group and others demonstrated that the AMP-activated protein kinase (AMPK), which is known as a central regulator of cell metabolism, plays a protective role in the vasculature. Since PGC-1alpha is one of the most important downstream targets of AMPK, we hypothesize that a deletion of endothelial PGC-1alpha impairs vascular function during angiotensin II infusion and that changes in NO signaling / oxidative stress (hypothesis 1) or vascular inflammation (hypothesis 3) play a key role in this process. In vivo application of the mitochondrial targeted antioxidant mitoTEMPO should determine whether mitochondrial reactive oxygen species are causally involved in this process. In two additional protocols we plan to investigate the role of PGC-1alpha regarding the vascular protective effects of exercise. We hypothesize that endothelial PGC-1alpha may affect exercise-mediated changes in vascular reactive oxygen species production and NO-signaling (hypothesis 2), which may account for PGC-1alpha related changes in neoangiogenesis and vascular aging (hypothesis 4).

转录共激活因子 PGC-1α 在线粒体生物合成和功能中发挥着重要作用。我们小组和其他小组的数据表明，AMP 激活蛋白激酶 (AMPK) 被称为细胞代谢的中央调节因子，在脉管系统中发挥保护作用。由于 PGC-1α 是 AMPK 最重要的下游靶标之一，我们假设内皮 PGC-1α 的缺失会损害血管紧张素 II 输注期间的血管功能，并且 NO 信号/氧化应激（假设 1）或血管炎症（假设3）在此过程中发挥关键作用。线粒体靶向抗氧化剂 mitoTEMPO 的体内应用应确定线粒体活性氧是否因果参与该过程。在另外两个方案中，我们计划研究 PGC-1α 在运动的血管保护作用方面的作用。我们假设内皮PGC-1α可能影响运动介导的血管活性氧产生和NO信号传导的变化（假设2），这可能解释PGC-1α相关的新血管生成和血管老化的变化（假设4）。

项目成果

PGC-1α dictates endothelial function through regulation of eNOS expression

PGC-1α 通过调节 eNOS 表达来决定内皮功能

• DOI: 10.1038/srep38210
• 发表时间: 2016-12-02
• 期刊: Scientific Reports
• 影响因子: 4.6
• 作者: Craige SM;Kröller-Schön S;Li C;Kant S;Cai S;Chen K;Contractor MM;Pei Y;Schulz E;Keaney JF Jr
• 通讯作者: Keaney JF Jr