Abstract 14201: Angiogenic Effects of Local Sustained Release of MicroRNA-126 in Murine Hindlimb Ischemia
Introduction: Recent studies demonstrate that microRNAs hold a promising potential in therapeutic intervention including angiogenesis. microRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related protein 1 (SPRED-1), an endogenous inhibitor of vascular endothelial growth factor (VEGF) signaling pathway. In this study, we investigated angiogenic effects of local sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model.
Methods: We induced mice unilateral hindlimb ischemia by left femoral artery resection. We randomly assigned the mice in 2 groups and performed intramuscular injection of miR-126-loaded PLGA-NPs or scrambled miR-loaded PLGA-NPs just after induction of ischemia.
Results: miR-126 expression levels in ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA-NPs compared to those with scrambled miR, indicating fair efficiency of local miR transduction (P<0.05, n=6). Laser doppler perfusion imaging revealed that limb blood flow in mice treated with miR-126-loaded PLGA-NPs were significantly higher at 14 days after treatment (P<0.0001, n=12). Immunohistochemical analysis indicated that CD31-positive cell density and α-smooth muscle actin-positive vessel density were significantly higher in miR-126-treated mice (P<0.01, n=6). SPRED-1 mRNA expression levels were significantly lower in miR-126-treated mice (P<0.05, n=6). Western blotting indicated that protein levels of pERK/ERK involved in VEGF signaling pathway were significantly higher in miR-126-treated mice (P<0.05, n=6), possibly due to the reduction of SPRED-1 levels in miR-126-treated mice (P<0.05, n=6).
Conclusion: miR-126 increased neovascularization, and thus improved tissue perfusion in a murine hindlimb ischemia. The present study suggests that local sustained release of miR-126-loaded PLGA-NPs might be an effective method in therapeutic angiogenesis for limb ischemia.
Author Disclosures: S. Tsumaru: None. K. Minakata: None. H. Masumoto: None. K. Ono: None. M. Izuhara: None. K. Yamazaki: None. T. Ikeda: None. R. Sakata: None.
- © 2016 by American Heart Association, Inc.