In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis

Djamel Lebeche, Roger Kaprielian, Federica Del Monte, Gordon Tomaselli, Judith K. Gwathmey, Arnold Schwartz, Roger J. Hajjar

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Prolongation of the action potential duration (APD) and decreased transient outward K+ current (Ito] have been consistently observed in cardiac hypertrophy. The relation between electrical remodeling and cardiac hypertrophy in vivo is unknown. Methods and Results - We studied rat hearts subjected to pressure overload by surgical ascending aortic stenosis (AS) and simultaneously infected these hearts with an adenovirus carrying either the Kv4.3 gene (Ad.Kv4.3) or the β-galactosidase gene (Ad.β-gal). Ito density was reduced and APD50 was prolonged (Pto density, and shorten APD50 by 1.6-fold, 5.3-fold, and 3.6-fold, respectively (Pto, APD prolongation, and cardiac hypertrophy occur early after AS, and in vivo gene transfer of Kv4.3 can restore these electrical parameters and abrogate the hypertrophic response via the calcineurin pathway.

Original languageEnglish (US)
Pages (from-to)3435-3443
Number of pages9
JournalCirculation
Volume110
Issue number22
DOIs
StatePublished - Nov 30 2004

Keywords

  • Gene therapy
  • Hypertrophy
  • Ion channels
  • Potassium
  • Stenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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