JACC: Basic to Translational Science (Dec 2016)

Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction

  • Tijana Knezevic, PhD,
  • Valerie D. Myers, MS,
  • Feifei Su, MD, PhD,
  • JuFang Wang, MD,
  • Jianliang Song, MD, PhD,
  • Xue-Qian Zhang, MD,
  • Erhe Gao, MD, PhD,
  • Guofeng Gao, MD, PhD,
  • Muniswamy Madesh, PhD,
  • Manish K. Gupta, PhD,
  • Jennifer Gordon, PhD,
  • Kristen N. Weiner, BS,
  • Joseph Rabinowitz, PhD,
  • Frederick V. Ramsey, PhD,
  • Douglas G. Tilley, PhD,
  • Kamel Khalili, PhD,
  • Joseph Y. Cheung, MD, PhD,
  • Arthur M. Feldman, MD, PhD

DOI
https://doi.org/10.1016/j.jacbts.2016.08.008
Journal volume & issue
Vol. 1, no. 7
pp. 647 – 656

Abstract

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Mutations in Bcl-2–associated athanogene 3 (BAG3) were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3) significantly (p < 0.0001) improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca2+]i and increased [Ca2+]i transient amplitudes, and increased maximal L-type Ca2+ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

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