Roles of physical exercise-induced MiR-126 in cardiovascular health of type 2 diabetes

Although physical activity is widely recommended for preventing and treating cardiovascular complications of type 2 diabetes mellitus (T2DM), the underlying mechanisms remain unknown. MicroRNA-126 (miR-126) is an angiogenetic regulator abundant in endothelial cells (ECs) and endothelial progenitor cells (EPCs). It is primarily involved in angiogenesis, inflammation and apoptosis for cardiovascular protection. According to recent studies, the levels of miR-126 in the myocardium and circulation are affected by exercise protocol. High-intensity interval training (HIIT) or moderate-and high-intensity aerobic exercise, whether acute or chronic, can increase circulating miR-126 in healthy adults. Chronic aerobic exercise can effectively rescue the reduction of myocardial and circulating miR-126 and vascular endothelial growth factor (VEGF) in diabetic mice against diabetic vascular injury. Resistance exercise can raise circulating VEGF levels, but it may have a little influence on circulating miR-126. The Several targets of miR-126 have been suggested for cardiovascular fitness, such as sprouty-related EVH1 domain-containing protein 1 (SPRED1), phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), vascular cell adhesion molecule 1 (VCAM1), high-mobility group box 1 (HMGB1), and tumor necrosis factor receptor-associated factor 7 (TRAF7). Here, we present a comprehensive review of the roles of miR-126 and its downstream proteins as exercise mechanisms, and propose that miR-126 can be applied as an exercise indicator for cardiovascular prescriptions and as a preventive or therapeutic target for cardiovascular complications in T2DM.