instmctions): Core B will be responsible for providing porcine models of myocardial infarction to each of the 3 projects in this PPG. Core Functions: A. To generate a pig Ml model with cardiac structural and functional derangements for all projects. B. To measure changes in cardiac structure and function after Ml. C. To treat Ml pigs (with AAV or drugs) and insert BrdU-containing minipumps as described in each of the projects, and measure the effects on cardiac structure and function. D. To provide the 3 projects with fixed tissue, isolated myocytes and frozen tissue for project specific experiments. Each of the three projects within this PPG will explore fundamental aspects of cardiac dysfunction induced by myocardial infarction in pigs. This animal model will be used because it has critical physiological features that mimic human biology. In addition, the Ml model to be used induces changes in cardiac structure and function that approximate conditions in humans with ischemic heart disease. Core B will supply investigators with a reliable, well characterized animal model so that each project can explore the mechanism they think is critical to heart failure induction and progression. Core B will also treat animals with agents that each of the 3 projects think will blunt or reverse the pathological consequences of Ml. At the completion of each study, Core B will prepare pig heart tissue (and blood) for histology, molecular biology and cell function analysis. These samples and data will be available to all projects.

Public Health Relevance

This Core will establish a large animal model of cardiac dysfunction, for testing of novel therapies for ischemic heart disease. This animal model has characteristics that are similar to humans. These features of the model system should allow our results to be translated into novel therapies for patients who have had a myocardial infarction and have a poor prognosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL108806-03
Application #
8650321
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Temple University
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
de Lucia, Claudio; Gambino, Giuseppina; Petraglia, Laura et al. (2018) Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure. Circ Heart Fail 11:e004153
Harper, Shavonn C; Johnson, Jaslyn; Borghetti, Giulia et al. (2018) GDF11 Decreases Pressure Overload-Induced Hypertrophy, but Can Cause Severe Cachexia and Premature Death. Circ Res 123:1220-1231
Cannavo, Alessandro; Koch, Walter J (2018) GRK2 as negative modulator of NO bioavailability: Implications for cardiovascular disease. Cell Signal 41:33-40
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
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
Schumacher, Sarah M; Koch, Walter J (2017) Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling. J Cardiovasc Pharmacol 70:129-141
Sharp 3rd, Thomas E; Kubo, Hajime; Berretta, Remus M et al. (2017) Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci 2:669-683
Sharp 3rd, Thomas E; Schena, Giana J; Hobby, Alexander R et al. (2017) Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction. Circ Res 121:1263-1278
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
Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott et al. (2016) Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects? Circ Res 118:1143-50; discussion 1150

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