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dc.contributor.authorIzuhara, Masayasuja
dc.contributor.authorKuwabara, Yasuhideja
dc.contributor.authorSaito, Naritatsuja
dc.contributor.authorYamamoto, Erikaja
dc.contributor.authorHakuno, Daihikoja
dc.contributor.authorNakashima, Yasuhiroja
dc.contributor.authorHorie, Takahiroja
dc.contributor.authorBaba, Osamuja
dc.contributor.authorNishiga, Masatakaja
dc.contributor.authorNakao, Tetsushija
dc.contributor.authorNishino, Tomohiroja
dc.contributor.authorNakazeki, Fumikoja
dc.contributor.authorIde, Yuyaja
dc.contributor.authorKimura, Masahiroja
dc.contributor.authorKimura, Takeshija
dc.contributor.authorOno, Kohja
dc.contributor.alternative桑原, 康秀ja
dc.contributor.alternative齋藤, 成達ja
dc.contributor.alternative中島, 康弘ja
dc.contributor.alternative堀江, 貴裕ja
dc.description.abstractBackground: Despite recent progress with drug-eluting stents, restenosis and thrombosis after endovascular intervention are still major limitations in the treatment of cardiovascular diseases. These problems are possibly caused by inappropriate inhibition of neointimal formation and retardation of re-endothelialization on the surface of the stents. miR-126 has been shown to have the potential to enhance vascular endothelial cell proliferation. Methods and results: We designed and constructed a 27-nt double strand RNA (dsRNA) conjugated to cholesterol, which has high membrane permeability, and formed mature miR-126 after transfection. For site-specific induction of miR-126, we utilized poly (DL-lactide-co-glycolide) nanoparticles (NPs). miR-126-dsRNA-containing NPs (miR-126 NPs) significantly reduced the protein expression of a previously identified miR-126 target, SPRED1, in human umbilical vascular endothelial cells (HUVECs), and miR-126 NPs enhanced the proliferation and migration of HUVECs. On the other hand, miR-126 NPs reduced the proliferation and migration of vascular smooth muscle cells, via the suppression of IRS-1. Finally, we developed a stent system that eluted miR-126. This delivery system exhibited significant inhibition of neointimal formation in a rabbit model of restenosis. Conclusions: miR-126 NP-conjugated stents significantly inhibited the development of neointimal hyperplasia in rabbits. The present study may indicate the possibility of a novel therapeutic option to prevent restenosis after angioplasty.ja
dc.publisherPublic Library of Scienceja
dc.rights© 2017 Izuhara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ja
dc.titlePrevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit modelja
dc.type.niitypeJournal Articleja
dc.identifier.jtitlePLOS ONEja
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