Adipose-derived mesenchymal stem cells alleviating heart dysfunction through suppressing MG 53 protein in rat model of diabetic cardiomyopathy

Objective: To investigate the effects of mesenchymal stem cells on cardiac injury and heart dysfunction induced by metabolic disorders as well as the underlying mechanisms including the expression of MG53--muscle specific E3 ligase Mitsugumin 53 in diabetic cardiomyopathy (DCM) in rats. Methods and results: We used a high-fat diet combined with low dose of streptozotocin administration to induce the diabetic cardiomyopathy model in rats, and performed four infusions of adipose-derived mesenchymal stem cells (ADMSCs). Here, we found that the hyperglycemia and cardiac dysfunction weresignificantly alleviated in the ADMSCs treated group compared to DCM group, as manifested by reduced blood glucose, improved systolic and diastolic heart function, inhibited interstitial fibrosis and myocardial hypertrophy, and prevented cardiomyocytes injury. DCM rats showed a significantly increased expression of MG53, and decreased insulin receptor (IR), insulin receptor substrate 1 (IRS1), and serine phosphorylation of Akt (p-Akt), which exhibited opposite changes to the ADMSCs treated group. In vitro, we simulated cardiac injury via 33 mmol/L glucose, used adipose-derived mesenchymal stem cells culture-medium to interfere with primary cardiomyocytes induced by 33 mmol/L glucose. The ADMSCs-CM treated group exhibited decreased expression of MG53, increased IR, IRS1, and p-Akt protein levels, with the differences being significant. Conclusions: Our results indicate that hyperglycemia is an independent risk factor for DCM, and MG53 plays a crucial role in the cardiac injury in the diabetic rat model. Furthermore, ADMSCs can alleviate the cardiac injury and improve heart dysfunction of DCM rats, involving their ability to downregulate the overexpression of MG53, and further elevate IR, IRS1, and p-Akt protein levels, which could improve insulin sensitivity and cardiac metabolism.