Protecting Myocardium by Enhancing Mitochodrial Integrity
通过增强线粒体完整性来保护心肌
基本信息
- 批准号:7908673
- 负责人:
- 金额:$ 204.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-01 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant):
During the preceding decade numerous interventional maneuvers that induce or inhibit remodeling, promote or prevent cell death, and damage or repair the heart have been described. Although successfully resolved in experimental models by managing signal transduction, implementing strategies to treat heart failure in a clinical setting requires more than creating a litany of molecular candidates. Successful treatment on a molecular level will depend, in large part, upon an integrated perspective of cellular survival under stress. Combinatorial modeling of cardiac survival signaling reveals many paths with a shared destination: protection of mitochondrial integrity. However, significant controversies persist regarding mechanisms of mitochondrial protection, with the interrelationships of molecules that mediate mitochondrial protection remaining largely unexplored. This Program Project addresses limitations in current understanding of myocardial cellular survival with opportunities for profound advances in conceptual and mechanistic approaches for mitigation of cardiomyopathic diseases characterized by cell death including ischemia, infarction, decompensation, and aging. While seemingly diverse, these conditions share loss of mitochondrial function and cell death as unifying characteristics that are inextricably linked. As such, our investigative team focuses upon a central goal: determining mechanisms that preserve mitochondrial integrity to enhance cellular survival and ultimately maintain cardiac function. Synergistic Program Components facilitate a multifaceted approach using novel methodologies to assess survival signaling and the impact of manipulating protective pathways upon mitochondria. Coordinated programmatic research will discover new regulatory mechanisms of mitochondrial function, cellular survival, and integration of heretofore disparate or unrecognized molecular elements into an essential unified perspective. Combined organ, cellular, and molecular approaches are essential for comprehensive and unequivocal validation of mechanisms leading to protection of mitochondria, and our emerging paradigm integrating cellular signaling, survival, and mitochondrial function reveals a web of co-dependent factors. Collectively, the factors, relationships, and consequences revealed by this Program Project will provide critical contextual knowledge for designing translational approaches amenable to rapid implementation of clinical treatment for heart disease.
描述(由申请人提供):
在过去的十年中,已经描述了诱导或抑制重塑,促进或预防细胞死亡以及损害或修复心脏的许多介入操作。尽管通过管理信号转导成功在实验模型中成功解决,但在临床环境中实施治疗心力衰竭的策略不仅需要创建一连串的分子候选者。在分子水平上的成功治疗将在很大程度上取决于在压力下的细胞存活的整合视角。心脏存活信号的组合建模揭示了许多具有共同目的地的路径:线粒体完整性的保护。然而,关于线粒体保护机制的重大争议持续存在,介导线粒体保护的分子的相互关系仍然在很大程度上没有探索。该计划项目解决了当前对心肌细胞存活的局限性,并在概念和机理方法方面取得了深远的进步,以缓解以细胞死亡为特征的心肌病疾病,包括缺血,梗死,失败和衰老。尽管看似多样,但这些条件与线粒体功能和细胞死亡的丧失是密不可分的统一特征。因此,我们的调查团队侧重于一个中心目标:确定保持线粒体完整性以增强细胞生存并最终维持心脏功能的机制。协同程序组件促进了使用新方法来评估生存信号传导和操纵保护途径对线粒体的影响的多方面方法。协调的程序研究将发现线粒体功能,细胞存活以及迄今不同或未识别的分子元素的新调节机制。结合器官,细胞和分子方法对于导致线粒体保护的机制的综合和明确验证至关重要,而我们的新兴范式整合了细胞信号传导,生存和线粒体功能,揭示了共同依赖性因子的网络。总的来说,该计划项目所揭示的因素,关系和后果将为设计转化方法提供关键的上下文知识,可快速实施心脏病的临床治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MARK ALAN SUSSMAN其他文献
MARK ALAN SUSSMAN的其他文献
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