Abstract
BackgroundAged 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.MethodsIn 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.ResultsThe 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.ConclusionsIn 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.
Highlights
Cardiovascular disease (CVD) is a common disease in the elderly
Previous studies found that the Wnt/β-catenin pathway can be reactivated after MI and contributes to the modulation of pathophysiological processes, including ventricular remodeling, cardiomyocyte apoptosis, and myocardial fibrosis [3,4,5]
In vivo effects of Soluble frizzled related protein 1 (Sfrp1) on histology and cardiac function of aged mice with acute myocardial ischemia (AMI) AAV-Sfrp1 was injected to generate the overexpression of Sfrp1; the infection efficiency of AAV-Sfrp1 was examined 5 weeks after the first injection by immunoblotting (Fig. 2a)
Summary
Cardiovascular disease (CVD) is a common disease in the elderly. The prevalence of atherosclerotic coronary artery disease (CAD) increases with increasing age, affecting more than half of those aged 60 years or older [1]. In addition to the increased prevalence of acute myocardial ischemia (AMI), elderly patients are associated with increasing levels of illness and death and worse prognosis, and a more effective treatment for AMI is currently in need [2]. Previous studies found that the Wnt/β-catenin pathway can be reactivated after MI and contributes to the modulation of pathophysiological processes, including ventricular remodeling, cardiomyocyte apoptosis, and myocardial fibrosis [3,4,5]. Effectively inhibiting the Wnt/βcatenin pathway may have important therapeutic value within the prevention and treatment of AMI injury in elderly patients [8, 9]. 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. We investigated potent targets related to Wnt/β-catenin pathway deregulation for AMI injury treatment
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