Impact of Leptin of Heart Failure and Survival after Myocardial Infarction

描述(由申请人提供)： 这份提案描述了一项为期5年的培训计划，目的是为了在中国发展学术生涯 心血管疾病。首席调查员(PI)在#年完成了有组织的研究金培训。 他是匹兹堡大学心脏病学教授，并将通过部门间合作扩展他的科学技能。该计划强调通过研究瘦素信号在心脏中的重要性，在大体和分子水平上进行心脏生理学、病理学、内分泌学和生化方面的培训。查尔斯·麦克蒂尔南博士是心血管研究所(CVI)的副教授，也是心力衰竭(HF)和细胞因子研究领域公认的领导者。克里斯托弗·奥唐奈博士，肺科副教授，是研究瘦素和心力衰竭小鼠生理学的专家。McTiernan博士和O‘Donnell博士在过去一起培养了大量的学生和研究员，并将指导PI的科学发展。为了加强培训，并提供科学和职业建议，将成立一个跨部门咨询委员会。CVI助理教授Michael Mathier博士将提供关于小鼠心力衰竭功能评估的培训。生物化学助理教授罗伯特·奥多尔蒂博士将在瘦素生理学、信号转导和cre-lox技术领域提供指导。病理学助理教授豪尔赫·塞普尔韦达博士是心脏病理学领域的专家，将提供与瘦素组织病理学相关的技术培训。提出的这项研究是基于初步数据，这些数据表明瘦素对心肌梗死后的心功能和存活率有好处。因此，我们假设瘦素在m1后具有保护作用。旨在测试这一压倒一切的假说并提供瘦素益处的机制理解的特定目标 1)观察瘦素缺乏和全身性瘦素替代对小鼠存活和心力衰竭发生发展的影响。2)比较ob/ob小鼠全身性和中枢性应用瘦素对m1后心衰的发生和存活的影响。3)检测心脏特异性Leptin受体缺失对心力衰竭大鼠生存和发展的影响。总体而言，UPMC的CVI通过鼓励跨学科合作和共享生产性科学发现所需的资源，为培训内科科学家提供了理想的环境。 (摘要结束)

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in Cardiovascular Disease. The principal investigator (PI) has completed structured fellowship training in Cardiology at the University of Pittsburgh and will expand upon his scientific skills through interdepartmental collaboration. This plan emphasizes training in cardiac physiology, pathology, endocrinology, and biochemistry at the gross and molecular levels through investigation of the importance of leptin signaling in the heart. Dr. Charles McTiernan is an Associate Professor in the Cardiovascular Institute (CVI) and a recognized leader in the field of heart failure (HF) and cytokine research. Dr. Christopher O'Donnell, Associate Professor in the Pulmonary Division, is an expert on the study of leptin and murine physiology in heart failure. Together, both Drs. McTiernan and O'Donnell have trained numerous students and fellows in the past and will mentor the Pi's scientific development. To enhance training and provide scientific and career advise, an interdepartmental advisory committee will be formed. Dr. Michael Mathier, Assistant Professor in the CVI, will provide training on the functional assessment of heart failure in mice. Dr. Robert O'Doherty, Assistant Professor in Biochemistry, will provide guidance in the areas of leptin physiology, signal transduction, and cre-lox technology. Dr. Jorge Sepulveda, Assistant Professor of Pathology, is an expert in the field of cardiac pathology and will provide training in techniques related to leptin histopathology. The research proposed is based on preliminary data that shows benefit to leptin on cardiac function and survival after myocardial infarction (Ml). Therefore, we hypothesize that leptin is protective after Ml. Specific aims designed to test this over-riding hypothesis and provide mechanistic understanding of leptin's benefit after Ml include using mice to: 1) Examine of the effect of leptin-deficiency and systemic leptin replacement on survival and the development of HF after Ml. 2) Compare systemic versus central effects of leptin administration in ob/ob mice on survival and the development of HF after Ml. 3) Examine the effect of cardiac specific deletion of the leptin receptor on survival and the development of HF after Ml. Overall, the CVI at UPMC provides an ideal environment for training physician scientists by encouraging inter-disciplinary collaboration and sharing of resources necessary for productive scientific discovery. (End of Abstract)