MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model

MicroRNA-145 (miR-145) reportedly alters the phenotype of vascular smooth muscle cells (VSMCs) from a proliferative to a contractile state. So far, viral or plasmid vectors have been experimentally used to transduce microRNAs into VSMCs. We hypothesized that a simple ex vivo microRNA delivery system using miR–145-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA NPs) could control the VSMC phenotype and prevent intimal hyperplasia. Jugular vein grafts of male Japanese white rabbits were soaked in phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NP solution or miR–145-loaded PLGA NP solution for 30 minutes (n = 8 for each). Vein grafts were implanted in the ipsilateral carotid artery and assessed 2 weeks after the implantation. Quantitative polymerase chain reaction analysis showed significantly higher miR-145 expression in the miR–145-treated group. The neointimal area was significantly smaller in the miR–145-treated group (phosphate-buffered saline-treated vs cont–miR-treated vs miR–145-treated group; 1.63 ± 0.52 mm2 vs 1.67 ± 0.49 mm2 vs 0.88 ± 0.34 mm2, respectively; P