Impact of Leptin of Heart Failure and Survival after Myocardial Infarction

描述（由申请人提供）： 该提案描述了一个为期5年的培训计划，以发展学术生涯， 心血管疾病主要研究者（PI）已完成结构化研究金培训， 他将通过跨部门合作扩大他的科学技能。该计划强调通过研究瘦素信号在心脏中的重要性，在总体和分子水平上进行心脏生理学，病理学，内分泌学和生物化学方面的培训。Charles McTiernan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的公认领导者。克里斯托弗奥唐纳博士，肺科副教授，是心力衰竭中瘦素和小鼠生理学研究的专家。McTiernan博士和奥唐纳博士过去一起培训了许多学生和研究员，并将指导Pi的科学发展。为了加强培训和提供科学和职业咨询，将成立一个跨部门咨询委员会。Michael Mathier博士，CVI助理教授，将提供关于小鼠心力衰竭功能评估的培训。Robert O 'Doherty博士，生物化学助理教授，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。所提出的研究是基于显示瘦素对心肌梗死（MI）后的心脏功能和存活有益的初步数据。因此，我们假设瘦素在MI后是保护性的。旨在检验这一压倒一切的假设，并提供瘦素的好处机制的理解的具体目标 包括使用小鼠：1）检查瘦素缺乏和全身性瘦素替代对MI后存活和HF发展的影响。2)比较肥胖基因野生型小鼠中瘦素给药对MI后存活和HF发展的全身与中枢效应。3)检查心肌特异性瘦素受体缺失对MI后存活和HF发展的影响。总的来说，在UPMC的CVI提供了一个理想的环境，通过鼓励跨学科的合作和资源共享必要的生产性科学发现，培养医生科学家。 (End摘要）

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)