Core C, the Heart/Cell Function Core, is going to serve projects 1-3 in this Program Project Grant to fulfill the following functions: 1. To establish reliable and economical mouse myocardial infarction models by permanently or temporarily ligating the left anterior descending coronary artery. These models will be the flatform for testing the therapeutical treatments in all projects to offer proof-of-concepts for further tests in large mammal (porcine) models; 2. To study in vivo cardiac function changes after Ml injury by echocardiography (weekly) and invasive intraventricular hemodynamic measurements (at the end of each study). These measurements will offer reproducible assessments of the efficacy of all treatments; 3. To isolate and characterize cardiac myocyte function to explore the cellular mechanisms of the potential beneficial effects of the therapeutical modalities as proposed in each project. 4. To centralize tissue and cell samples (mouse and pig) for each project. In this core, we will fix or freeze tissue or isolated cell samples after the treatment is done. These samples will be collected and kept in a centralized and well-maintained facility. The samples will be distributed for each project upon request. 5. To prepare histological samples for all projects. 6. To prepare tissues for molecular analysis and perform these studies when needed. In summary. Core C will provide essential support for all projects in this Project Program Project in an economical while scientifically reliable and efficient way.

Public Health Relevance

Myocardial infarction is a significant health problem with few effective therapies to slow or reverse the pathological structural and functional remodeling that it induces. This core will produce reliable mouse model systems for investigators in projects to study. This core will also prepare cells and tissues from pigs (Core B) for investigators in all 3 projects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL108806-01A1
Application #
8299666
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-05-07
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$229,500
Indirect Cost
$79,500
Name
Temple University
Department
Type
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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
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; 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
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

Showing the most recent 10 out of 73 publications