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Title: Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model
Authors: Izuhara, Masayasu
Kuwabara, Yasuhide
Saito, Naritatsu
Yamamoto, Erika
Hakuno, Daihiko
Nakashima, Yasuhiro
Horie, Takahiro
Baba, Osamu
Nishiga, Masataka
Nakao, Tetsushi
Nishino, Tomohiro
Nakazeki, Fumiko
Ide, Yuya
Kimura, Masahiro
Kimura, Takeshi
Ono, Koh
Author's alias: 桑原, 康秀
齋藤, 成達
中島, 康弘
堀江, 貴裕
Issue Date: 2-Mar-2017
Publisher: Public Library of Science
Journal title: PLOS ONE
Volume: 12
Issue: 3
Thesis number: e0172798
Abstract: Background: 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.
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.
URI: http://hdl.handle.net/2433/218961
DOI(Published Version): 10.1371/journal.pone.0172798
PubMed ID: 28253326
Appears in Collections:Journal Articles


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