Abstract 15965: BAG3 Rescues Contractile Dysfunction Post-MI: Cellular Mechanism

Mutations in BAG3 underlie the development of heart failure with reduced ejection fraction (HFrEF). However, little is known regarding molecular mechanisms of BAG3 in the heart. Methods: To dissect the role of BAG3 in the heart, mice underwent ligation of the left main coronary artery (MI) or sham surgery. 8 weeks later, MI and Sham mice were randomized to receive either AAV9-GFP (Sham-GFP, MI-GFP) or GFP-tagged-AAV9-BAG3 (MI-BAG3) by intra-orbital injection. Cardiac myocytes were isolated 3 wks later and cellular markers of calcium homeostasis were examined. Results: MI-GFP mice demonstrated reduced EF and decreased BAG3 (Fig1 A-C) as compared to MI-BAG3 and Sham-GFP mice. Similarly, contraction amplitudes of isolated myocytes were significantly lower in MI-GFP than in Sham-GFP cells, differences were amplified with ISO. Cell shortening and re-lengthening velocities were significantly improved post-MI by AAV9-BAG3. Similarly, systolic [Ca2+]i was significantly lower with ISO in the MI-GFP, but AAV9-BAG3 ...