Abstract:

Objective This study aimed to investigate the role of the ubiquitin specific protease-7（USP7）in promoting cardiomyocyte proliferation and improving cardiac function following heart transplantation. Methods An adeno-associated virus serotype 9（AAV9）-mediated USP-7 overexpression system and a small-molecule activator，MS-8，were used in a mouse heart transplantation model to assess the effects of USP-7 on cardiomyocyte proliferation and graft function. Ki67，phospho-histone H3（pH3）and AuroraB immunofluorescence staining were performed to evaluate the proliferative capacity of cardiomyocytes. Cardiac function of the transplanted hearts was assessed by echocardiography，andhistological analyses were conducted to examine the structural integrity of the myocardium. Results RNA-seq analysis showed that USP-7 expression gradually decreased during cardiac development，while its activation significantly enhanced cardiomyocyte proliferation，as indicated by increased Ki67- and pH3-positive cell ratios. In the mouse heterotopic heart transplantation model，echocardiographic evaluation demonstrated that USP-7 overexpression markedly improved cardiac systolic function. Conclusion USP-7 promotes cardiomyocyte proliferation and protects cardiac graft function，thereby facilitating post-transplant myocardial repair. These findings identify USP-7 as a potential molecular target for regenerativetherapy after heart transplantation. 

Key words:

Ubiquitin specific protease-7, Cardiomyocytes, Heart transplantation, AAV9, Cardiacfunction preservation

摘要：

关键词:

 , 泛素特异性蛋白酶 -7 , 心肌细胞 , 心脏移植 , 9 型腺相关病毒 , 心功能保护 ,