Abstract

Based on the hypothesis that nitric oxide (NO) is released during exercise, the applicant has proposed to delineate the molecular mechanisms of exercise preconditioning (PC) by examining the role of NO in signal transduction. The goal of the research will be achieved by addressing five Specific Aims : (i) by establishing the role of PKCe in exercise PC; (ii) by establishing the role of the Src family of protein tyrosine kinase in exercise PC; (iii) by identifying the specific transcription factors responsible for the transcriptional upregulation of iNOS and the development of exercise PC; (iv) by establishing the role of PKCe-Src/Lck signaling pathway in the recruitment of the transcription factors responsible for exercise PC; and (v) by studying the role of each individual NOS isoform in triggering and mediating exercise PC and elucidating its post-translational modulation. The results of this study will shed new light on the mechanisms of exercise PC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL055757-08
Application #
6537246
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Balshaw, David M
Project Start
1995-05-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
8
Fiscal Year
2002
Total Cost
$447,445
Indirect Cost

  Institution

Name
University of Louisville
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292

  Publications

Tang, Xian-Liang; Li, Qianhong; Rokosh, Gregg et al. (2016) Long-Term Outcome of Administration of c-kit(POS) Cardiac Progenitor Cells After Acute Myocardial Infarction: Transplanted Cells Do not Become Cardiomyocytes, but Structural and Functional Improvement and Proliferation of Endogenous Cells Persist for at L Circ Res 118:1091-105
Muthusamy, Senthilkumar; DeMartino, Angelica M; Watson, Lewis J et al. (2014) MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression. J Biol Chem 289:29665-76
Bolli, Roberto; Tang, Xian-Liang; Sanganalmath, Santosh K et al. (2013) Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation 128:122-31
Zafir, Ayesha; Readnower, Ryan; Long, Bethany W et al. (2013) Protein O-GlcNAcylation is a novel cytoprotective signal in cardiac stem cells. Stem Cells 31:765-75
Sanganalmath, Santosh K; Bolli, Roberto (2013) Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res 113:810-34
Stein, Adam B; Bolli, Roberto; Dawn, Buddhadeb et al. (2012) Carbon monoxide induces a late preconditioning-mimetic cardioprotective and antiapoptotic milieu in the myocardium. J Mol Cell Cardiol 52:228-36
Zuba-Surma, Ewa K; Guo, Yiru; Taher, Hisham et al. (2011) Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction. J Cell Mol Med 15:1319-28
Lefer, David J; Bolli, Roberto (2011) Development of an NIH consortium for preclinicAl AssESsment of CARdioprotective therapies (CAESAR): a paradigm shift in studies of infarct size limitation. J Cardiovasc Pharmacol Ther 16:332-9
Li, Qianhong; Guo, Yiru; Ou, Qinghui et al. (2011) Gene transfer as a strategy to achieve permanent cardioprotection II: rAAV-mediated gene therapy with heme oxygenase-1 limits infarct size 1 year later without adverse functional consequences. Basic Res Cardiol 106:1367-77
Tang, Xian-Liang; Sanganalmath, Santosh K; Sato, Hiroshi et al. (2011) Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction. PLoS One 6:e25320

Showing the most recent 10 out of 125 publications