HIF-1α-induced up-regulation of microRNA-126 contributes to the effectiveness of exercise training on myocardial angiogenesis in myocardial infarction rats

Exercise training (ET) is a non-drug natural rehabilitation approach for myocardial infarction (MI). Among the numerous beneficial effects of ET, myocardial angiogenesis is indispensable. In the present study, we investigated the role and mechanism of HIF-1 alpha and miR-126 in ET-induced MI myocardial angiogenesis which may provide new insights for MI treatment. Rat model of post-MI and human umbilical vein endothelial cells (HUVECs) were employed for our research. Histomorphology, immunohistochemistry, quantitative real-time PCR, Western blotting and small-interfering RNA (siRNA) transfection were applied to evaluate the morphological, functional and molecular mechanisms. In vivo results showed that 4-week ET could significantly increase the expression of HIF-1 alpha and miR-126 and reduce the expression of PIK3R2 and SPRED1, while 2ME2 (HIF-1 alpha inhibitor) partially attenuated the effect of ET treatment. In vitro results showed that HIF-1 alpha could trigger expression of miR-126 in HUVECs in both normoxia and hypoxia, and miR-126 may be involved in the tube formation of HUVECs under hypoxia through the PI3K/AKT/eNOS and MAPK signalling pathway. In conclusion, we revealed that HIF-1 alpha, whose expression experiences up-regulation during ET, could function as an upstream regulator to miR-126, resulting in angiogenesis promotion through the PI3K/AKT/eNOS and MAPK signalling pathway and subsequent improvement of the MI heart function.