Adeno-associated virus-mediated gene delivery of Perm1 enhances cardiac contractility in mice

被引:0
|
作者
Sreedevi, Karthi [1 ,4 ]
Zaitsev, Alexey V. [1 ,4 ]
Doku, Abigail [1 ,2 ,4 ]
Thomas, Rebekah [1 ,2 ,4 ]
James, Amina [1 ,3 ,4 ]
Do, Sara [1 ,4 ]
Zhang, Mei [9 ]
Sedovy, Meghan W. [1 ,2 ,4 ]
Leng, Xinyan [1 ,4 ]
Dennison, Clare L. [1 ,4 ,8 ]
Johnstone, Scott R. [1 ,4 ,5 ,6 ]
Kirk, Jonathan A. [7 ]
Yan, Zhen [3 ,9 ]
Warren, Junco S. [1 ,3 ,4 ]
机构
[1] Virginia Tech, Fralin Biomed Res Inst, Virginia Tech Caril, Roanoke, VA 24016 USA
[2] Virginia Tech, Translat Biol Med & Hlth Grad Program, Blacksburg, VA USA
[3] Virginia Tech, Dept Human Nutr Food & Exercise, Blacksburg, VA 24016 USA
[4] Virginia Tech, Fralin Biomed Res Inst, Ctr Vasc & Heart Res, Roanoke, VA 24016 USA
[5] Virginia Tech, Coll Sci, Dept Biol Sci, Roanoke, VA USA
[6] Virginia Tech, Caril Sch Med, Dept Surg, Roanoke, VA USA
[7] Loyola Univ Chicago, Dept Cell & Mol Physiol, Chicago, IL USA
[8] Virginia Tech, Tissue Proc Core Fralin Biomed Res Inst, Roanoke, VA USA
[9] Virginia Tech Caril, Fralin Biomed Res Inst, Ctr Exercise Med Res, Roanoke, VA USA
关键词
AAV; cardiac contractility; mitochondrial bioenergetics; PERM1; troponin C; CONFOCAL MICROSCOPY; OXIDATIVE CAPACITY; TISSUE;
D O I
10.1152/ajpheart.00545.2024
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 the 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.
引用
收藏
页码:H1112 / H1118
页数:7
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