1. Core Functions Mouse Physiology and Phenotyping: The small animal physiology core will provide two major services to all four of the projects in this PPG: 1) pathological and physiological models of cardiac hypertrophy and heart failure in mice, and 2) complete and comprehensive phenotyping of wild type and genetically modified mice. Mouse Models systems include: A) Mechanically- induced pressure overload hypertrophy and heart failure using the technique of transverse aortic constriction (TAC), both chronic and intermittent. B) Myocardial Infarction C) Genetic models of heart failure: muscle LIM protein knock out (MLP[-/-]) and calsequestrin (CSQ) overexpression. D) Swimming and running exercise. Mouse Phenotyping will include: A) An in-depth analysis of in vivo cardiac function by serial echocardiography in conscious mice. B) In vivo measurements of intrinsic myocardial contractility by pressure-volume (PV) loop analysis. C) In vivo end-systolic myocardial stress using stress-strain relations. D) In vivo PAR responsiveness by catheter derived hemodynamics. E) Invasive and non-invasive blood pressure recordings and exercise capacity by programmed treadmill testing. F) Ambulatory electrocardiographic telemetry. G) Ex vivo measurements of isolated myocyte contractility. The leaders of this core have been involved in the development of numerous surgical and genetic models of cardiac hypertrophy and heart failure. The Pi's laboratory has considerable expertise in a wide-ranging array of methodologies for the phenotyping of mice. The PI has also been involved in the development of a number of genetic and surgical models of heart failure. For example, microsurgical procedures and hemodynamic evaluation of pressure overload hypertrophy induced through transverse aortic constriction developed by the PI, is now a standard method used by many laboratories around the world.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL075443-08
Application #
8382601
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
8
Fiscal Year
2012
Total Cost
$228,801
Indirect Cost
$82,133
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Cannavo, Alessandro; Rengo, Giuseppe; Liccardo, Daniela et al. (2017) ?1-Blockade Prevents Post-Ischemic Myocardial Decompensation Via ?3AR-Dependent Protective Sphingosine-1 Phosphate Signaling. J Am Coll Cardiol 70:182-192
Schumacher, Sarah M; Koch, Walter J (2017) Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling. J Cardiovasc Pharmacol 70:129-141
Lai, Thung-S; Lindberg, Robert A; Zhou, Hua-Lin et al. (2017) Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide. Sci Rep 7:16163
Waldschmidt, Helen V; Homan, Kristoff T; Cato, Marilyn C et al. (2017) Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. J Med Chem 60:3052-3069
Eisner, Verónica; Cupo, Ryan R; Gao, Erhe et al. (2017) Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity. Proc Natl Acad Sci U S A 114:E859-E868
Bouley, Renee; Waldschmidt, Helen V; Cato, M Claire et al. (2017) Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors. Mol Pharmacol 92:707-717
Jean-Charles, Pierre-Yves; Yu, Samuel Mon-Wei; Abraham, Dennis et al. (2017) Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of ?-adrenergic receptor signaling. JCI Insight 2:
Elphinstone, Robyn E; Besla, Rickvinder; Shikatani, Eric A et al. (2017) S-Nitrosoglutathione Reductase Deficiency Confers Improved Survival and Neurological Outcome in Experimental Cerebral Malaria. Infect Immun 85:
Waldschmidt, Helen V; Homan, Kristoff T; Cruz-Rodríguez, Osvaldo et al. (2016) Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem 59:3793-807
Zhang, Rongli; Hess, Douglas T; Reynolds, James D et al. (2016) Hemoglobin S-nitrosylation plays an essential role in cardioprotection. J Clin Invest 126:4654-4658

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