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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
7P01HL074237-05
Application #
7462319
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2007
Total Cost
$273,891
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Lanfear, David E; Gibbs, Joseph J; Li, Jia et al. (2017) Targeted Metabolomic Profiling of Plasma and Survival in Heart Failure Patients. JACC Heart Fail 5:823-832
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Sabbah, Hani N; Gupta, Ramesh C; Kohli, Smita et al. (2016) Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure. Circ Heart Fail 9:e002206
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Meraviglia, Viviana; Azzimato, Valerio; Colussi, Claudia et al. (2015) Acetylation mediates Cx43 reduction caused by electrical stimulation. J Mol Cell Cardiol 87:54-64
Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E et al. (2015) Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy. J Am Coll Cardiol 66:139-53
Lanfear, David E; Li, Jia; Abbas, Raza et al. (2015) Genetic Factors Influencing B-type Natriuretic Peptide-Mediated Production of Cyclic Guanosine Monophosphate and Blood Pressure Effects in Heart Failure Patients. J Cardiovasc Transl Res 8:545-53
Kop, Willem J; Galvao, Tatiana F; Synowski, Stephen J et al. (2015) Effects of environmental stress following myocardial infarction on behavioral measures and heart failure progression: The influence of isolated and group housing conditions. Physiol Behav 152:168-74
Roul, David; Recchia, Fabio A (2015) Metabolic alterations induce oxidative stress in diabetic and failing hearts: different pathways, same outcome. Antioxid Redox Signal 22:1502-14

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