Studies on Myocyte Apoptosis in Congestive Heart Failure

描述(由申请人提供)： 这位候选人是医学助理教授Detlef Wencker博士，他加入了耶鲁大学心脏血管内科和心力衰竭移植计划部门，以继续他过去的研究努力，长期目标是成为一名独立的研究人员。在之前工作的基础上，他选择研究人类心力衰竭(CHF)的基本机制，以找到针对疾病细胞起源的新治疗模式。耶鲁大学凭借其出色的临床和基础科学研究环境，再加上斯图尔特·卡茨博士高效的指导，使候选人处于完成这项任务的有利地位。这一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并巩固他的临床和基础科学知识来继续他的研究事业发展。这项拟议的研究试图确定细胞凋亡在终末期扩张型心肌病患者心力衰竭失代偿中的作用。初步数据表明，在急性充血性心力衰竭恶化期间，骨骼肌细胞凋亡上调。目的1探讨骨骼肌肌细胞凋亡从稳定代偿性心力衰竭到急性心脏失代偿的动态过程。第二个目标假设，骨骼肌中的细胞凋亡动力学与心脏中的类似。候选人将纵向监测CHF患者在代偿和急性心力衰竭加重时骨骼肌和心肌标本中的凋亡率、促凋亡性炎症细胞因子水平和凋亡调节因子的状态。具体目标3将检查中重度CHF患者使用促红细胞生成素(一种具有强大的抗凋亡特性的糖蛋白)治疗是否可以防止心肌细胞丢失，从而延缓失代偿性CHF的发展。所产生的结果将对骨骼肌和心肌细胞凋亡在急性充血性心力衰竭失代偿过程中的作用产生关键的见解。这些数据有可能转化为更有效、更具临床相关性的CHF治疗方法。 (摘要结束)

DESCRIPTION (provided by applicant): The candidate, Dr. Detlef Wencker, Assistant Professor of Medicine, joined the Section of Cardio-vascular Medicine and Heart Failure transplant 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 1 will 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. (End of Abstract)