Cardiac Energy Metabolism in Heart Failure

心力衰竭中的心脏能量代谢

基本信息

批准号：
8532015
负责人：
HANI N SABBAH
金额：
$ 212.37万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8532015
关键词：
Address Adrenergic Agents Algorithms Animal Model Animals Area Attenuated Bioenergetics Canis familiaris Carbohydrates Cardiac Chemicals Chronic Clinical Complex Congenital Heart Defects Consumption Coronary Coupled Cyclic AMP Cyclic AMP-Dependent Protein Kinases Cytosol DNA Development Devices Diet Dietary Carbohydrates Dietary Fats Dietary Intervention Dietary Supplementation Dilated Cardiomyopathy Electrons Energy Metabolism Enzymes Equilibrium Event Extravasation Failure Fatty acid glycerol esters Functional disorder Funding Genes Genetic Glucose Goals Grant Heart Heart Mitochondria Heart Rate Heart failure Histology Human Hydrogen Peroxide Inner mitochondrial membrane Intake Lead Left Left Ventricular Dysfunction Left Ventricular Function Left Ventricular Remodeling Link Macronutrients Nutrition Manganese Superoxide Dismutase Membrane Metabolic Metabolism Mitochondria Mitochondrial Matrix Modeling Modification Molecular Muscle Mitochondria Myocardial Myocardium NADP Nutritional Outcome Outer Mitochondrial Membrane Oxidases Oxidative Phosphorylation Oxidative Stress Oxygen Consumption Pacemakers Pentosephosphate Pathway Performance Polyunsaturated Fatty Acids Process Production Program Research Project Grants Proteins Pump RNA Reactive Oxygen Species Research Research Personnel Research Project Grants Role Serine Signal Pathway Skeletal Muscle Structure Superoxides Testing Therapeutic Threonine Transgenic Mice Translational Research Ventricular Ventricular Remodeling Viral Vector Voltage-Dependent Anion Channel Work Yeast Model System adrenergic base beta-adrenergic receptor clinically relevant cytochrome c oxidase design gain of function glucose metabolism heart metabolism improved knock-down loss of function mitochondrial dysfunction mouse model novel overexpression oxidative damage polyunsaturated fat pressure prevent programs research study response stem sugar treatment strategy vagus nerve stimulation

项目摘要

This Program Project Grant addresses the metabolic mechanisms underlying the pathophysiology of heart failure (HF), and aims to identify novel metabolic approaches to prevent and treat HF. The consequences of metabolic dysfunction in HF are poorly understood, but there is strong evidence that energy metabolism can effect contractile function and progressive left ventricular remodeling. This translational research project uses sophisticated animal models of HF to evaluate novel mechanisms that link various aspects of cardiac metabolism to clinically relevant outcomes. This application will investigate fundamental questions about the pathophysiology of HF, and the effects of manipulating energy metabolism on cardiac function and HF progression. This Program Project is composed of four projects: Project 1: "Impact of Macronutrient Intake in Heart Failure". The effects of dietary fat, protein and carbohydrate composition on progression of HF will be investigated. Project 2: "Heart Rate Control, Myocardial Energetics and Progression of Heart Failure". This project will dissect the role of heart rate in abnormalities of cardiac energetics and progression of LV dilation and dysfunction in HF. Project 3: "Substrate Selection and Oxidative Stress in Heart Failure". Causal relationships will be explored between altered energy substrate metabolism and oxidative stress in HF. Project 4: "Mitochondrial Dysfunction in Heart Failure". This project investigates the molecular mechanisms for the decrease in oxidative phosphorylation found in heart and skeletal muscle mitochondria in HF. In addition, there will be four Cores (Administrative, Large Animal/Histology, Metabolism, and Mitochondria/Mass Spec).

该计划项目赠款旨在解决心力衰竭病理生理学（HF）的代谢机制，旨在鉴定预防和治疗HF的新型代谢方法。 HF中代谢功能障碍的后果知之甚少，但是有强有力的证据表明能量代谢可以影响收缩功能和进行性左心室重塑。该转化研究项目使用HF的复杂动物模型来评估将心脏代谢的各个方面与临床相关结果联系起来的新型机制。该应用将研究有关HF病理生理学的基本问题，以及操纵能量代谢对心脏功能和HF进展的影响。该计划项目由四个项目组成：项目1：“大量营养素摄入在心力衰竭中的影响”。饮食脂肪，蛋白质和碳水化合物组成对HF进展的影响。项目2：“心率控制，心肌能量学和心力衰竭进展”。该项目将剖析心率在心脏能量异常中的作用以及HF中LV扩张和功能障碍的进展。项目3：“心力衰竭中的底物选择和氧化应激”。在HF中，能量底物代谢的改变和氧化应激之间将探索因果关系。项目4：“心力衰竭的线粒体功能障碍”。该项目研究了在HF中在心脏和骨骼肌线粒体中发现的氧化磷酸化降低的分子机制。此外，还将有四个核心（行政，大动物/组织学，代谢和线粒体/质量规格）。

项目成果

期刊论文数量（104）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vagus nerve stimulation in experimental heart failure.

DOI：
10.1007/s10741-010-9209-z
发表时间：
2011-03
期刊：
HEART FAILURE REVIEWS
影响因子：
4.6
作者：
Sabbah, Hani N.;Ilsar, Itamar;Zaretsky, Asaph;Rastogi, Sharad;Wang, Mengjun;Gupta, Ramesh C.
通讯作者：
Gupta, Ramesh C.

Chronic treatment with trimetazidine reduces the upregulation of atrial natriuretic peptide in heart failure.

曲美他嗪的长期治疗可减少心力衰竭时心房钠尿肽的上调。

DOI：
10.1111/j.1472-8206.2006.00424.x
发表时间：
2006
期刊：
Fundamental & clinical pharmacology
影响因子：
2.9
作者：
Morgan,EricE;Young,MartinE;McElfresh,TracyA;Kung,TheodoreA;Hoit,BrianD;Chandler,MargaretP;Stanley,WilliamC
通讯作者：
Stanley,WilliamC

Metabolic therapy for heart disease: impact of trimetazidine.

心脏病的代谢治疗：曲美他嗪的影响。

DOI：
10.1007/s10741-005-7541-5
发表时间：
2005
期刊：
Heart failure reviews
影响因子：
4.6
作者：
Sabbah,HaniN;Stanley,WilliamC
通讯作者：
Stanley,WilliamC

Revascularization of hibernating myocardium: uneven reflorescence after the drought.

冬眠心肌的血运重建：干旱后不均匀的再花。

DOI：
10.1016/j.jacc.2014.12.024
发表时间：
2015
期刊：
Journal of the American College of Cardiology
影响因子：
24
作者：
Recchia,FabioA
通讯作者：
Recchia,FabioA

Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

DOI：
10.1371/journal.pone.0034402
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Khairallah RJ;Kim J;O'Shea KM;O'Connell KA;Brown BH;Galvao T;Daneault C;Des Rosiers C;Polster BM;Hoppel CL;Stanley WC
通讯作者：
Stanley WC