Submaximal walking increases MicroRNA-126 and angiogenic markers in men and women with peripheral arterial disease

PURPOSE: Vascular dysfunction is a pathophysiological mechanism in peripheral artery disease (PAD). PAD patients exhibit reduced circulating expression of microRNA-126 (c-miRNA-126) and VEGF. Submaximal walking (SW) is recommended in PAD because it increases walking capacity, partially by improving vascular regulation, which can be observed after a walking session. Nevertheless, previous studies were conducted with maximal walking and in men. As women with PAD present worse disease characteristics and greater ischemia, they may be less responsive to SW, which needs to be investigated. Thus, this study compared the acute effects of SW on vascular function, c-miRNA-126 and angiogenic markers in men and women with PAD. METHODS: Thirty patients (15 women) underwent, in a random order, 2 sessions: control (standing on treadmill) and SW (15 bouts of 2-min walking at moderate intensity intersected by 2-min rest). Circulating gene expression of miRNA-126, SPRED-1, PI3KR2, VEGF, and eNOS were evaluated before and after the interventions. RESULTS: Both genders presented similar maximal walking capacity. Vascular function did not change after the interventions in either gender. After SW, both groups presented a similar decrease in PI3KR2 and similar increases in c-miRNA-126, VEGF and eNOS. CONCLUSION: In men and women with PAD, an acute SW similarly increases c-miRNA-126 expression, which inhibits PI3KR2, enabling the progression of the VEGF angiogenic signaling pathway of PI3K-AKT-eNOS. These results support that SW is equally effective in inducing molecular angiogenic changes in men and women with PAD, supporting its recommendation for both genders. Future studies should address these possible chronic effects of walking.