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

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.