Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction

R. J. Hassink, H. Nakajima, H. O. Nakajima, P. A. Doevendans, L. J. Field

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). Objective: To determine whether the altered remodelling results in improved cardiac function in the MHC-1152stop mice after MI, as compared with non-transgenic mice. Methods: MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 h and at 4 weeks after MI, and left ventricular pressure-volume measurements were performed at 4 weeks after MI in infarcted and shamoperated animals. Results: Infarct size in MHC-1152stop mice and nontransgenic littermates was not statistically different at 24 h after MI, as measured by tetrazolium staining. Morphometric analysis showed that infarct scar expansion at 4 weeks after MI was reduced by 10% in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks after MI, the ventricular isovolumic relaxation time constant (τ) was decreased by 19% (p<0.05), and the slope of the dP/dtmax-EDV relationship was increased 99% (p<0.05), in infarcted MHC-1152stop mice as compared with infarcted non-transgenic littermates. Conclusion: Expression of the dominant interfering p193 transgene results in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks after MI. Antagonism of p193 activity may represent an important strategy for the treatment of MI.

Original languageEnglish (US)
Pages (from-to)1159-1164
Number of pages6
JournalHeart
Volume95
Issue number14
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction'. Together they form a unique fingerprint.

  • Cite this