Mechanical unloading of the heart activates the calpain system

Peter Razeghi, Kaelin C. Volpini, Mou Er Wang, Keith A. Youker, Stanislaw Stepkowski, Heinrich Taegtmeyer

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The mechanism for the decrease in cardiomyocyte size with mechanical unloading is unknown. The calpain system regulates cardiomyocyte atrophy. We obtained samples from failing human hearts at the time of implantation and explantation of a left ventricular assist device. For mechanical unloading, we also heterotopically transplanted rat or mouse hearts for 1 week. The effect of calpain inhibition on cardiac atrophy was assessed in transplanted hearts overexpressing calpastatin. We measured transcript levels of calpain 1 and 2 in the human and the rodent model, as well as calpain activity, a calpain-specific degradation product and cardiomyocyte size in the two rodent models. Mechanical unloading of the failing human heart significantly increased calpain 2 gene expression. Transcript levels of calpain 1 and 2, calpain activity and a calpain-specific degradation product all significantly increased in the unloaded rat heart. Unexpectedly, in hearts of animals overexpressing calpastatin, cardiomyocyte size also decreased. Mechanical unloading of the mammalian heart activates the calpain system, although other proteolytic systems may compensate for decreased calpain activity when calpastatin is overexpressed.

Original languageEnglish (US)
Pages (from-to)449-452
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume42
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • LVAD
  • Protein degradation
  • Reverse remodeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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