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.
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.
|Schumacher, Sarah M; Koch, Walter J (2017) Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling. J Cardiovasc Pharmacol 70:129-141|
|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|
|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|
|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|
|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|
|Rengo, Giuseppe; Pagano, Gennaro; Filardi, Pasquale Perrone et al. (2016) Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure. Circ Res 118:1116-24|
|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|
|Zhang, Xiaoying; Ai, Xiaojie; Nakayama, Hiroyuki et al. (2016) Persistent increases in Ca(2+) influx through Cav1.2 shortens action potential and causes Ca(2+) overload-induced afterdepolarizations and arrhythmias. Basic Res Cardiol 111:4|
|Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang et al. (2016) BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes. J Mol Cell Cardiol 92:10-20|
|Traynham, Christopher J; Hullmann, Jonathan; Koch, Walter J (2016) ""Canonical and non-canonical actions of GRK5 in the heart"". J Mol Cell Cardiol 92:196-202|
Showing the most recent 10 out of 70 publications