title: Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model.
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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Izuhara
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kuwabara
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Naritatsu
authors.initials: N
authors.lastname: Saito
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Daihiko
authors.initials: D
authors.lastname: Hakuno
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horie
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Baba
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nishiga
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishino
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nakazeki
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ide
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
mesh_terms: D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D054855:Drug-Eluting Stents; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D053758:Nanoparticles / Q000737:chemistry*; D058426:Neointima / Q000517:prevention & control*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
chemical_list: D004337:Drug Carriers; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D012330:RNA, Double-Stranded; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002784:Cholesterol