Studies on Myocyte Apoptosis in Congestive Heart Failure

充血性心力衰竭心肌细胞凋亡的研究

• 批准号: 7018402
• 负责人: DETLEF WENCKER
• 金额: $ 15.93万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018402
• 关键词: BCL2 gene /protein; Bax gene /protein; CD95 molecule; apoptosis; cardiac myocytes; circulatory assist; clinical research; clinical trials; congestive heart failure; cytokine; cytoprotection; drug screening /evaluation; erythropoietin; heart disorder chemotherapy; heart ventricle; human subject; human therapy evaluation; hypertrophic myocardiopathy; interleukin 6; muscle cells; pathologic process; patient oriented research; striated muscles; tumor necrosis factor alpha

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)

描述（由申请人提供）： 该候选人是医学助理教授 Detlef Wencker 博士，加入耶鲁大学心血管医学和心力衰竭移植项目部，以继续他过去的研究工作，并以成为一名独立研究者的长期目标为目标。作为他之前工作的延伸，他选择研究人类心力衰竭 (CHF) 的基本机制，以便找到针对该疾病的细胞起源的新治疗方式。耶鲁大学拥有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。该奖项将使候选人能够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职业发展。拟议的研究旨在确定细胞凋亡在终末期扩张型心肌病患者失代偿性 CHF 中的作用。初步数据表明，CHF 急性加重期间骨骼肌细胞凋亡上调。目标 1 将研究以下假设：骨骼肌的肌细胞凋亡经历从稳定、代偿性 CHF 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细胞凋亡动力学相似。候选人将在CHF代偿期和急性CHF恶化期纵向监测CHF患者骨骼和心肌标本中的细胞凋亡率、促凋亡炎症细胞因子的水平以及细胞凋亡调节因子的状态。具体目标 3 将检查用促红细胞生成素（一种具有有效抗细胞凋亡特性的糖蛋白）治疗中度至重度 CHF 患者是否可以防止心肌细胞损失，从而延缓失代偿性 CHF 的发展。产生的结果将为急性 CHF 失代偿期间骨骼和心肌细胞凋亡的作用提供重要见解。这些数据有可能转化为更有效、临床相关的慢性心力衰竭治疗方法。 （摘要完）