miR-221 Regulation Mechanism of Aerobic Exercise Ameliorating High-Fat Diet-Induced Endothelial Structural Damage

Objective: To investigate the ameliorative effect of aerobic exercise on endothelial injury in mice fed a high-fat diet and the regulated mechanism of the miR-221. Methods: The HF and HFE group received a prepared high fat diet. After 8 weeks, the exercise groups were subjected to aerobic exercise on a running platform. Body weight, serum lipid levels, TNF-α, aortic structure, eNOS protein and mRNA levels and miR-221 levels were measured in each group of mice separately; Cell culture assays for the regulation of eNOS expression by TNF-α and miR-221. Results: Aerobic exercise significantly decreased the body weight, TC, TG, LDL-C, and TNF-α and a significant increase in HDL-C in high-fat diet-fed mice. After aerobic exercise, the intima/(intima + media) ratio was significantly decreased in the HFE group. Moreover, exercise suppressed overexpression of miR-221 induced by high-fat diet, with a concomitant increase in eNOS protein and mRNA expressions. Cell culture experiments revealed that miR-221 played a regulatory role in eNOS protein expression, and TNF-α inhibited eNOS proteins by inducing miR-221 overexpression. Conclusions: Aerobic exercise significantly improved endothelial dysfunction induced by high-fat diets in mice, in which post-translational regulation of eNOS expression by miR-221 plays an important role.