MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit
Hiroomi Nishio1, Hidetoshi Masumoto1, Kazuhisa Sakamoto1
1Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Background:
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.
Methods:
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.
Results:
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 < .01 for the miR-145-treated vs the cont-miR-treated group). In the miR-145-treated group, Ki-67-positive cells were significantly fewer, indicating lower VSMC proliferation. An inflammation-related molecule, CD40 expression was significantly reduced by miR-145-loaded PLGA NP treatment.
Conclusions:
Local and sustained release of miR-145 by PLGA NPs attenuated intimal hyperplasia in the rabbit model by maintaining VSMCs in a contractile state. This simple ex vivo miR-145 delivery system would be promising toward broader clinical application.
Insights
This study demonstrates that ex vivo delivery of microRNA-145 (miR-145) using poly(lactic-co-glycolic acid) nanoparticles effectively reduces vascular smooth muscle cell proliferation and prevents intimal hyperplasia in a rabbit model.
Area of Science:
- Biomedical Engineering
- Vascular Biology
- Nanomedicine
Background:
- MicroRNA-145 (miR-145) influences vascular smooth muscle cell (VSMC) phenotype, shifting it from proliferative to contractile.
- Current methods for microRNA delivery into VSMCs, such as viral or plasmid vectors, have limitations.
Purpose of the Study:
- To investigate the efficacy of a novel ex vivo microRNA delivery system using miR-145-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs).
- To assess the potential of this system to control VSMC phenotype and prevent intimal hyperplasia.
Main Methods:
- Jugular vein grafts from rabbits were incubated with either phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NPs, or miR-145-loaded PLGA NPs.
- The treated vein grafts were implanted into the carotid artery and analyzed after two weeks.
Main Results:
- Quantitative PCR confirmed significantly higher miR-145 expression in the miR-145-treated group.
- The neointimal area was significantly reduced in the miR-145-treated group compared to controls (0.88 mm² vs. 1.67 mm²).
- miR-145 treatment led to fewer Ki-67-positive cells, indicating reduced VSMC proliferation, and decreased expression of the inflammation marker CD40.
Conclusions:
- Local and sustained delivery of miR-145 via PLGA NPs effectively attenuated intimal hyperplasia in a rabbit model.
- This ex vivo delivery approach promotes VSMC maintenance in a contractile state, showing promise for clinical applications.
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