MicroRNA-210 improves perfusion recovery following hindlimb ischemia via suppressing reactive oxygen species.

ABSTRACT

In peripheral arterial disease (PAD), angiogenesis is a major process involved in repairing the microvasculature in the ischemic lower limb. MicroRNA-210 (miR-210) is a microRNA that is substantially increased in patients with PAD. However, the effects of miR-210 on angiogenesis following PAD remain elusive. In the present study, mice with hindlimb ischemia (HLI) were generated as an animal model of PAD, and miR-210 levels were overexpressed in the ischemic limb. The overexpression of miR-210 using microRNA mimics greatly improved angiogenesis and perfusion recovery; in contrast, the knockdown of miR-210 impaired perfusion recovery 28 days after HLI. Ischemic muscle tissue was harvested 7 days after experimental PAD in order to perform biochemical tests, and miR-210 antagonism resulted in increased malondialdehyde levels. In cultured endothelial cells under simulated ischemia, miR-210 mimic improved endothelial cell viability and enhanced tube formation; and a miR-210 inhibitor decreased cell survival, reduced tube formation and increased reactive oxygen species (ROS) levels. Furthermore, miR-210 antagonism increased the protein disulfide-isomerase levels in cultured endothelial cells. These results demonstrate that ischemia-induced miR-210 elevation is adaptive in PAD, and that miR-210 improves angiogenesis at least partially through decreasing ROS production.