Co-expression of skeletal and cardiac troponin T decreases mouse cardiac function

Q. Q. Huang, H. Z. Feng, J. Liu, J. Du, L. B. Stull, C. S. Moravec, X. Huang, J. P. Jin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

In contrast to skeletal muscles that simultaneously express multiple troponin T (TnT) isoforms, normal adult human cardiac muscle contains a single isoform of cardiac TnT. To understand the significance of myocardial TnT homogeneity, we examined the effect of TnT heterogeneity on heart function. Transgenic mouse hearts overexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT was investigated in vivo and ex vivo as an experimental system of concurrent presence of two classes of TnT in the adult cardiac muscle.This model of myocardial TnT heterogeneity produced pathogenic phenotypes: echocardiograph imaging detected age-progressive reductions of cardiac function; in vivo left ventricular pressure analysis showed decreased myocardial contractility; ex vivo analysis of isolated working heart preparations confirmed an intrinsic decrease of cardiac function in the absence of neurohumoral influence. The transgenic mice also showed chronic myocardial hypertrophy and degeneration. The dominantly negative effects of introducing a fast TnT into the cardiac thin filaments to produce two classes of Ca 2+ regulatory units in the adult myocardium suggest that TnT heterogeneity decreases contractile function by disrupting the synchronized action during ventricular contraction that is normally activated as an electrophysiological syncytium.

Original languageEnglish (US)
Pages (from-to)C213-C222
JournalAmerican Journal of Physiology - Cell Physiology
Volume294
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Echocardiography
  • Myocardial heterogeneity
  • Transgenic mouse
  • Working heart preparation

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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