Studies on Myocyte Apoptosis in Congestive Heart Failure

候选人Detlef Wencker博士，医学助理教授，加入了心血管科 耶鲁大学的医学和心脏衰竭移植项目，以继续他过去的研究 他的长期目标是成为一名独立的调查员。在他先前工作的延伸中， 他选择研究人类心力衰竭（CHF）的基本机制，以发现新的 靶向疾病的细胞起源的治疗方式。耶鲁大学以其杰出的临床 和基础科学研究环境，再加上Stuart Katz博士的高效指导 使候选人处于完成这项任务的有利地位。该奖项将允许候选人 通过获得生物统计学公共卫生硕士学位， 巩固他的临床和基础科学知识。 这项研究旨在确定细胞凋亡在心力衰竭患者失代偿中的作用。 晚期扩张型心肌病初步数据表明，骨骼肌细胞凋亡是 在CHF急性加重期间上调。目的1探讨心肌细胞凋亡与心肌细胞凋亡的关系。 骨骼肌经历了从稳定的代偿性CHF到急性心脏性CHF的动态过程， 代偿失调第二个目标假设骨骼肌细胞凋亡的动力学 与心脏相似。候选人将监测细胞凋亡的速率，促细胞凋亡的水平， 炎症细胞因子和凋亡调节因子在骨骼肌和心肌标本中的状态， CHF患者在代偿期和CHF急性加重期的纵向分布。具体目标3 将检查是否使用红细胞生成素（一种具有强效抗细胞凋亡特性的糖蛋白）治疗患者 中度至重度CHF的患者将防止肌细胞损失，因此延迟 失代偿性CHF。 产生的结果将产生关键的见解骨骼肌和心肌细胞凋亡的作用 急性CHF失代偿期这些数据有可能转化为更有效的， 相关CHF治疗。

The candidate, Dr. Detlef Wencker, Assistant Professor of Medicine, joined the Section of Cardiovascular Medicine and Heart Failurerfransplant Program at Yale University in order to carry on his past research endeavors with the long-term goal of becoming an independent investigator. In extension of his prior work, he has chosen to investigate the basic mechanism of heart failure (CHF) in humans in order to find new treatment modalities that target the cellular origin of the disease. Yale University with its outstanding clinical and basic science research environment combined with a highly effective mentorship by Dr. Stuart Katz places the candidate in a strong position to accomplish this task. This award will allow the candidate to continue his research career development by obtaining a Masters in Public Health in Biostatistics and by consolidating his knowledge of both clinical and basic science. The proposed research seeks to identify the role of apoptosis in decompensating CHF among patients with end-stage dilated cardiomyopathy. Preliminary data suggest that skeletal muscle apoptosis is upregulated during acute CHF exacerbation. Aim 1will investigate the hypothesis that myocyte apoptosis of the skeletal muscle undergoes a dynamic process from stable, compensated CHF to acute cardiac decompensation. The second aim hypothesizes that the dynamics of apoptosis in the skeletal muscle parallels that in the heart. The candidate will monitor the rate of apoptosis, the level of pro-apoptotic inflammatory cytokines and the state of apoptotic regulators in skeletal and cardiac muscle specimens of CHF patients longitudinally at times of compensation and times of acute CHF exacerbation. Specific aim 3 will examine if treatment with erythropoietin, a glycoprotein with potent anti-apoptotic properties, of patients with moderate to severe CHF will prevent myocyte cell loss and therefore delay the development of decompensated CHF. The results generated will yield critical insights into the role of skeletal and cardiac muscle apoptosis during acute CHF decompensation. These data have the potential to translate into more effective, clinically relevant CHF treatments.