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, Valerie D. Myers, Feifei Su, Ju Fang Wang, Jianliang Song, Xue Qian Zhang, Erhe Gao, Guofeng Gao, Madesh Muniswamy, Manish K. Gupta, Jennifer Gordon, Kristen N. Weiner, Joseph Rabinowitz, Frederick V. Ramsey, Douglas G. Tilley, Kamel Khalili, Joseph Y. Cheung, Arthur M. Feldman

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)647-656
Number of pages10
JournalJACC: Basic to Translational Science
Volume1
Issue number7
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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Keywords

  • BAG3
  • gene therapy
  • heart failure
  • left ventricular function
  • myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Knezevic, T., Myers, V. D., Su, F., Wang, J. F., Song, J., Zhang, X. Q., Gao, E., Gao, G., Muniswamy, M., Gupta, M. K., Gordon, J., Weiner, K. N., Rabinowitz, J., Ramsey, F. V., Tilley, D. G., Khalili, K., Cheung, J. Y., & Feldman, A. M. (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. JACC: Basic to Translational Science, 1(7), 647-656. https://doi.org/10.1016/j.jacbts.2016.08.008