Fatty Acid Oxidation in Heart Failure Progression

描述（由申请人提供）：衰竭的心脏不能有效地将食物燃烧产生的化学能转移到收缩工作中。心力衰竭中代谢功能障碍的后果尚不清楚，但有强有力的证据表明，能量代谢受损会导致收缩功能障碍和进行性左心室重构，这是心力衰竭状态的特征。本项目的主题是鉴定心力衰竭时心肌能量底物代谢异常，以及这些异常对左心室功能和重构的影响，以及疾病的进展。

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.