Abstract

Dilated cardiomyopathy is characterized by an enlarged, thin walled, poorly functioning heart. While this condition can be caused by a multiplicity of factors, one recognized etiology is chronic tachycardia. The goals of this project are: (1) identify the cellular and extracellular alterations responsible for the ventricular dilatation and dysfunction with developing cardiomyopathy, (2) quantify the residual ventricular dysfunction and abnormal geometry during the regression of dilated cardiomyopathy, and (3) examine the cellular and extracellular mechanisms potentially responsible for these permanent alterations. The applicant would perform a longitudal study using a pacing induced model of cardiomyopathy and recovery to: (a) measure the systolic and diastolic properties of the ventricular chamber, (b) compute changes in myocyte geometry, ultrastructural composition, function, and adhesion capacity, and (c) examine collagen content, type, distribution, geometric conformation, and gene expression of collagen types within the ventricular wall. In this way, the structural and functional changes to the ventricle could be directly related to cellular and extracellular events.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL045024-04
Application #
2221842
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1991-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Medical University of South Carolina
Department
Surgery
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425

  Publications

Mukherjee, Rupak; Snipes, Jonathan M; Saunders, Stuart M et al. (2012) Discordant activation of gene promoters for matrix metalloproteinases and tissue inhibitors of the metalloproteinases following myocardial infarction. J Surg Res 172:59-67
Mukherjee, Rupak; Zavadzkas, Juozas A; Rivers, William T et al. (2010) Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity. Am J Physiol Heart Circ Physiol 299:H217-24
Mukherjee, Rupak; Rivers, William T; Ruddy, Jean Marie et al. (2010) Long-term localized high-frequency electric stimulation within the myocardial infarct: effects on matrix metalloproteinases and regional remodeling. Circulation 122:20-32
Mukherjee, Rupak; McQuinn, Tim C; Dugan, Melissa A et al. (2010) Cardiac function and circulating cytokines after endotoxin exposure in neonatal mice. Pediatr Res 68:381-6
Mukherjee, Rupak; Colbath, Gregory P; Justus, Charles D et al. (2010) Spatiotemporal induction of matrix metalloproteinase-9 transcription after discrete myocardial injury. FASEB J 24:3819-28
Mukherjee, Rupak; Zavadzkas, Juozas A; Saunders, Stuart M et al. (2008) Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs. Ann Thorac Surg 86:1268-76
Deschamps, Anne M; Zavadzkas, Juozas; Murphy, Rebecca L et al. (2008) Interruption of endothelin signaling modifies membrane type 1 matrix metalloproteinase activity during ischemia and reperfusion. Am J Physiol Heart Circ Physiol 294:H875-83
Apple, Kimberly A; Yarbrough, William M; Mukherjee, Rupak et al. (2006) Selective targeting of matrix metalloproteinase inhibition in post-infarction myocardial remodeling. J Cardiovasc Pharmacol 47:228-35
Lindsey, Merry L; Escobar, G Patricia; Dobrucki, Lawrence W et al. (2006) Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Am J Physiol Heart Circ Physiol 290:H232-9
Mukherjee, Rupak; Apple, Kimberly A; Squires, Christina E et al. (2006) Protein kinase C isoform activation and endothelin-1 mediated defects in myocyte contractility after cardioplegic arrest and reperfusion. Circulation 114:I308-13

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