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
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Elsevier 2016-12-01 |
Deskripsi
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.