Jing Tao1,2, Xian Wei3, Ying Huang3, Fen Liu2, Yun Wu3, Dilare Adi3, Yang Xiang3, You Chen3, Yi-Tong Ma4,5, Bang-Dang Chen6,7. 1. Department of Cardiology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, China. 2. Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China. 3. Department of Cardiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China. 4. Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China. myt-xj@163.com. 5. Department of Cardiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China. myt-xj@163.com. 6. Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China. chenbangdang@126.com. 7. Department of Physiology, School of Preclinical Medicine, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People's Republic of China. chenbangdang@126.com.
Abstract
BACKGROUND: Aged patients suffering from acute myocardial ischemia (AMI) exhibit an increased mortality rate and worse prognosis, and a more effective treatment is currently in need. In the present study, we investigated potent targets related to Wnt/β-catenin pathway deregulation for AMI injury treatment. METHODS: In the present study, AAV-Sfrp1 was transduced into the myocardium of aged mice, and an AMI model was established in these aged mice to study the effect and molecular mechanism of Sfrp1 overexpression on AMI-induced injury. RESULTS: The results showed that Sfrp1 was successfully overexpressed in the myocardium of aged mice and remarkably reduced Wnt/β-catenin pathway activity in aged mice after AMI, effectively reducing the degree of myocardial fibrosis, inhibiting cardiomyocyte apoptosis, and improving cardiac function. We revealed that the exogenous introduction of Sfrp1 could be considered a promising strategy for improving post-AMI injury in aged mice by inhibiting Wnt/β-catenin pathway activity. CONCLUSIONS: In conclusion, the Wnt/β-catenin pathway potentially represents a key target in AMI in aged mice. Sfrp1 might be used as a small molecule gene therapy drug to improve heart function, reduce the degree of myocardial fibrosis, inhibit cardiomyocyte apoptosis and reduce AMI injury in aged mice by inhibiting the Wnt/β-catenin pathway, thereby effectively protecting aged hearts from AMI injury.
BACKGROUND: Aged patients suffering from acute myocardial ischemia (AMI) exhibit an increased mortality rate and worse prognosis, and a more effective treatment is currently in need. In the present study, we investigated potent targets related to Wnt/β-catenin pathway deregulation for AMI injury treatment. METHODS: In the present study, AAV-Sfrp1 was transduced into the myocardium of aged mice, and an AMI model was established in these aged mice to study the effect and molecular mechanism of Sfrp1 overexpression on AMI-induced injury. RESULTS: The results showed that Sfrp1 was successfully overexpressed in the myocardium of aged mice and remarkably reduced Wnt/β-catenin pathway activity in aged mice after AMI, effectively reducing the degree of myocardial fibrosis, inhibiting cardiomyocyte apoptosis, and improving cardiac function. We revealed that the exogenous introduction of Sfrp1 could be considered a promising strategy for improving post-AMI injury in aged mice by inhibiting Wnt/β-catenin pathway activity. CONCLUSIONS: In conclusion, the Wnt/β-catenin pathway potentially represents a key target in AMI in aged mice. Sfrp1 might be used as a small molecule gene therapy drug to improve heart function, reduce the degree of myocardial fibrosis, inhibit cardiomyocyte apoptosis and reduce AMI injury in aged mice by inhibiting the Wnt/β-catenin pathway, thereby effectively protecting aged hearts from AMI injury.
Entities:
Keywords:
Acute myocardial ischemia injury; Aging; Myocardial fibrosis; Soluble frizzled related protein 1 (Sfrp1); Wnt/β-catenin pathway
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