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: 7515441
• 负责人: DETLEF WENCKER
• 金额: $ 14.27万
• 依托单位: HARTFORD HOSPITAL
• 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/7515441
• 关键词: Acute; Aftercare; Apoptosis; Apoptotic; Award; Basic Science; Biometry; Biopsy; Cardiac; Cardiac Myocytes; Cardiovascular system; Cells; Cessation of life; Chronic; Clinical; Condition; Congestive Heart Failure; Data; Development; Device Removal; Dilated Cardiomyopathy; Disease; Early treatment; Environment; Erythropoietin; Financial compensation; Future; Glycoproteins; Goals; Heart; Heart Transplantation; Heart failure; Hematopoietic; Hormones; Hospitalization; Human; Inflammatory; Interleukin-6; Knowledge; Left; Left ventricular structure; Medicine; Mentorship; Modality; Modeling; Monitor; Mus; Muscle Cells; Myocardium; Numbers; Output; Pathogenesis; Patients; Performance; Play; Positioning Attribute; Primary idiopathic dilated cardiomyopathy; Principal Investigator; Process; Progressive Clinical Course; Property; Public Health; Rate; Receptor Signaling; Recovery; Research; Research Personnel; Risk; Role; Score; Severities; Skeletal Muscle; Skeletal system; Specimen; Staging; Stimulus; Syndrome; Time; Translating; Tumor Necrosis Factor Ligand Superfamily Member 6; Tumor Necrosis Factor-alpha; Universities; Work; career; cellular targeting; clinically relevant; cytokine; human TNF protein; implantation; improved; insight; prevent; professor; programs; ventricular assist device

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.

候选人 Detlef Wencker 博士，医学助理教授，加入心血管科 耶鲁大学医学和心力衰竭 fransplant 项目，以继续他过去的研究 努力成为一名独立调查员的长期目标。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，以便找到新的机制。 针对疾病的细胞起源的治疗方式。耶鲁大学以其出色的临床 基础科学研究环境与 Stuart Katz 博士高效的指导相结合 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和通过 巩固他的临床和基础科学知识。 拟议的研究旨在确定细胞凋亡在失代偿性 CHF 患者中的作用 患有终末期扩张型心肌病。初步数据表明骨骼肌细胞凋亡 CHF 急性恶化期间上调。目标 1 将研究心肌细胞凋亡的假设 骨骼肌经历从稳定、代偿性 CHF 到急性心脏病的动态过程 失代偿。第二个目标假设骨骼肌细胞凋亡的动态 与心中的那个相似。候选人将监测细胞凋亡率、促细胞凋亡水平 骨骼和心肌样本中炎症细胞因子和凋亡调节因子的状态 CHF 患者在代偿期和急性 CHF 恶化期的纵向分布。具体目标3 将检查患者是否接受促红细胞生成素（一种具有有效抗凋亡特性的糖蛋白）治疗 中度至重度CHF将阻止肌细胞损失，从而延缓CHF的发展 失代偿性 CHF。 产生的结果将为骨骼和心肌细胞凋亡的作用提供重要的见解 急性 CHF 失代偿期间。这些数据有可能转化为更有效的临床数据 相关 CHF 治疗。