Karthi Sreedevi, Alexey V Zaitsev, Abigail Doku, Rebekah Thomas, Amina James, Sara Do, Mei Zhang, Meghan W Sedovy, Xinyan Leng, Clare L Dennison, Scott R Johnstone, Jonathan A Kirk, Zhen Yan, Junco S Warren
Reduced muscle contractility and mitochondrial bioenergetics are the hallmarks of systolic heart failure. There is currently no therapy targeting both. Here, we show that gene delivery of Perm1 via adeno-associated virus (AAV) simultaneously enhances cardiac contractility and mitochondrial biogenesis in C57BL6 mice. Moreover, we found that PERM1 interacts with Troponin C (TnC), a key contractile protein in striated muscle, and that AAV- Perm1 led to upregulation of TnC. This study suggests that gene delivery of Perm1 may be a novel therapeutic approach to treat systolic heart failure by simultaneously restoring cardiac contractility and mitochondrial bioenergetics...
September 13, 2024: American Journal of Physiology. Heart and Circulatory Physiology