Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, Virginia, United States.
Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, Virginia, United States.
Am J Physiol Heart Circ Physiol. 2024 Oct 1;327(4):H1112-H1118. doi: 10.1152/ajpheart.00545.2024. Epub 2024 Sep 13.
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 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- led to the upregulation of TnC. This study suggests that gene delivery of may be a novel therapeutic approach to treat systolic heart failure by simultaneously restoring cardiac contractility and mitochondrial bioenergetics. gene delivered with AAV9 enhances cardiac contractility in mice, and it is concomitant with the increase of mitochondrial bioenergetics and upregulation of TnC. This is the first study showing that PERM1, previously known as a striated muscle-specific mitochondrial regulator, also positively regulates cardiac contractility.
心肌收缩力和线粒体生物能降低是收缩性心力衰竭的特征。目前尚无针对这两者的治疗方法。在这里，我们表明，通过腺相关病毒（AAV）进行 PERM1 基因传递可同时增强 C57BL6 小鼠的心肌收缩力和线粒体生物发生。此外，我们发现 PERM1 与肌钙蛋白 C（TnC）相互作用，TnC 是横纹肌中的关键收缩蛋白，而 AAV- 导致 TnC 的上调。这项研究表明，PERM1 的基因传递可能是通过同时恢复心肌收缩力和线粒体生物能来治疗收缩性心力衰竭的一种新的治疗方法。用 AAV9 传递的 PERM1 基因可增强小鼠的心肌收缩力，同时伴随着线粒体生物能的增加和 TnC 的上调。这是第一项表明以前被认为是横纹肌特异性线粒体调节剂的 PERM1 也可正向调节心肌收缩力的研究。
