Fatty Acid Oxidation in Heart Failure Progression

心力衰竭进展中的脂肪酸氧化

• 批准号: 7000634
• 负责人: HANI N SABBAH
• 金额: $ 23.45万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7000634
• 关键词: bioenergetics; heart failure; heart metabolism

DESCRIPTION (provided by applicant): The failing heart is unable to transfer effectively the chemical energy from the combustion of foodstuffs to contractile work. The consequences of metabolic dysfunction in heart failure are poorly understood, but there is strong evidence that impaired energy metabolism contributes to contractile dysfunction and to the progressive left ventricular remodeling that are characteristic of the heart failure state. The theme of this Program Project is the identification of abnormalities of myocardial energy substrate metabolism that occur with heart failure, and the effects of these abnormalities on left ventricular function and remodeling, and the progression of the disease. This Program consists of four projects and three core facilities. The projects are: Project 1: "Metabolic Regulation in Heart Failure" Project 2: "Fatty Acid Oxidation in Heart Failure Progression" Project 3: "Metabolic Phenotype Switch in Heart Failure" Project 4: "Mitochondrial Dysfunction in Heart Failure" The goal of all four projects is to identify the mechanisms regulating the metabolic changes that occur over the course of heart failure, and to elucidate the effects of these metabolic changes on contractile function and the progression of heart failure. Common questions are addressed by all projects regarding the mechanisms responsible for the alterations in metabolic phenotype in heart failure, and the consequences of these changes on cardiac function and progression of the disease. All studies will be performed in well-established large animal models of heart failure, and short and long-term manipulations of substrate metabolism will be used to elucidate the precise consequences of energy metabolism in the pathophysiology of heart failure. The major strength of this Program is the combination of in vivo studies on cardiac function and metabolism with the detailed assessment of biochemical regulators of cardiac phenotype and energy substrate metabolism.

描述（由申请人提供）：失败的心脏无法有效地将化学能从食品的燃烧转移到收缩工作。代谢功能障碍在心力衰竭中的后果知之甚少，但是有强有力的证据表明能量代谢受损会导致收缩功能障碍以及渐进性的左心室重塑，这是心力衰竭状态的特征。该计划项目的主题是鉴定心力衰竭发生的心肌底物代谢异常，以及这些异常对左心室功能和重塑的影响以及疾病的进展。 该计划由四个项目和三个核心设施组成。项目是： 项目1：“心力衰竭的代谢调节” 项目2：“心力衰竭进展中的脂肪酸氧化” 项目3：“心力衰竭中的代谢表型切换” 项目4：“心力衰竭的线粒体功能障碍” 所有四个项目的目标是确定调节心力衰竭过程中发生代谢变化的机制，并阐明这些代谢变化对收缩功​​能的影响和心力衰竭的发展。所有项目都解决了有关心力衰竭代谢表型改变的机制的解决，以及这些变化对心脏功能和疾病进展的后果。所有研究都将在已建立的大型心力衰竭的大型动物模型中进行，并且对底物代谢的短期和长期操纵将用于阐明能量代谢在心力衰竭病理生理学中的确切后果。该程序的主要优势是对心脏功能和代谢的体内研究以及对心脏表型生化调节剂和能量底物代谢的详细评估的结合。