Studies on Myocyte Apoptosis in Congestive Heart Failure

候选人，医学助理教授德特尔夫·温克博士，加入了心血管科 耶鲁大学医学和心脏衰竭移植计划，以继续他过去的研究 致力于成为一名独立调查员的长期目标。作为他先前工作的延伸， 他选择研究人类心力衰竭(CHF)的基本机制，以找到新的 针对疾病的细胞起源的治疗方式。耶鲁大学及其卓越的临床 和基础科学研究环境与斯图尔特·卡茨博士高效的指导相结合 使应聘者处于完成这项任务的有利地位。该奖项将允许候选人 继续他的研究事业发展，获得生物统计学公共卫生硕士学位和 巩固他在临床和基础科学方面的知识。 这项拟议的研究试图确定细胞凋亡在患者心力衰竭失代偿中的作用。 患有终末期扩张型心肌病。初步数据表明，骨骼肌细胞凋亡是 在急性充血性心力衰竭恶化期间上调。目的1探讨心肌细胞凋亡与心肌损伤的关系。 骨骼肌经历了从稳定的代偿性心力衰竭到急性心脏衰竭的动态过程。 失代偿。第二个目标假设骨骼肌中的细胞凋亡动力学 在心脏上也是如此。候选人将监测凋亡率，促凋亡水平 大鼠骨骼肌和心肌组织中炎性细胞因子和细胞凋亡调节因子的状态 CHF患者的纵向代偿时间和急性心力衰竭加重时间。具体目标3 将检查患者是否使用促红细胞生成素治疗，促红细胞生成素是一种具有强大抗细胞凋亡特性的糖蛋白 中重度CHF可防止心肌细胞丢失，从而延缓心力衰竭的发展 失代偿性心力衰竭。 所产生的结果将对骨骼肌和心肌细胞凋亡的作用产生关键的见解 在急性充血性心力衰竭失代偿期间。这些数据有可能在临床上转化为更有效的 相关充血性心力衰竭治疗。

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.