Abstract
The dysregulation of autophagy is related to a variety of cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R). Nerve growth factor (NGF) has been shown to have therapeutic potential in ischaemic heart injury. In this study, we demonstrate that NGF administration can accelerate autophagic flux and attenuate protein ubiquitination in myocardial I/R heart. Our results showed that NGF could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury. The protective effect of NGF is associated with the inhibition of autophagy related proteins. On another hand, NGF enhances the clearance of ubiquitinated protein and increases the survival of myocardial cell in vivo and in vitro. Additionally, NGF could activate the PI3K/AKT and mTOR signaling pathways. These results suggested that the cardioprotective effect of NGF is related to the restoration of autophagic flux and attenuation of protein ubiquitination via the activation of PI3K/AKT and mTOR pathway.
Highlights
Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, which has imposed a substantial burden on the society [1]
Our results showed that Nerve growth factor (NGF) could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury
After NGF treatment, the EF was reversed to 67.1 ± 3.9 % in the myocardial I/R animal model group, which was consistent to the FS results showing improved cardiac function
Summary
Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, which has imposed a substantial burden on the society [1]. The pathogenesis reflects the confluence of multiple aspects, including perturbation of inflammatory responses, ischemia, local edema, focal hemorrhage, free radical stress and ion homeostasis Despite these important progress, there is still a critical lack of successful solutions for prevent MIRI. Our previous studies using both in vivo and in vitro approaches showed that autophagy is a key player mediating progressive degeneration of the heart, which eventually contributes to the development of myocardial I/R injury [5]. These studies suggest that autophagy could be an effective drug gable target to improve myocardial I/R injury
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