The impact of proangiogenic microRNA modulation on blood flow recovery following hind limb ischemia. A systematic review and meta-analysis of animal studies

Pro-angiogenic microRNA modulation is a potentially attractive approach in the management of peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to examine the impact of microRNAs involved in the process of angiogenesis on blood flow recovery following hind limb ischemia induction in animal models.A literature search was performed to identify studies testing the efficacy of microRNA treatment on animal models of hind limb ischemia. Following that, a meta-analysis of the included studies was executed with the primary outcome being the change in ischemic-to-normal hind limb perfusion ratio assessed via laser Doppler imaging. Moreover, risk of bias, sensitivity analysis and publication bias were evaluated.Studies evaluation led to the inclusion of 18 studies whose meta-analysis suggested that microRNA treatment resulted in improved ischemic hind limb perfusion 7 [standardized mean difference (SMD): 0.93, 95% CI 0.49-1.38], 14 (SMD: 1.31, 95% CI 0.78-1.84), and 21 days (SMD: 1.13, 95% CI 0.59-1.66) after hind limb ischemia induction. Moderate-to-substantial heterogeneity and possible publication bias were noted. Risk of bias was unclear despite the balanced baseline animal characteristics.The present meta-analysis suggests that pro-angiogenic modulation of microRNAs accelerates vascular perfusion recovery in animal models of acute hind limb ischemia. Further studies on animal models with similar characteristics to that of PAD patients are warranted to translate those findings in human PAD setting.