Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model

Autor: Yuya Ide, Daihiko Hakuno, Takahiro Horie, Tomohiro Nishino, Osamu Baba, Fumiko Nakazeki, Koh Ono, Takeshi Kimura, Tetsushi Nakao, Yasuhide Kuwabara, Yasuhiro Nakashima, Naritatsu Saito, Masahiro Kimura, Masataka Nishiga, Masayasu Izuhara, Erika Yamamoto
Rok vydání: 2017
Předmět:
0301 basic medicine
Vascular smooth muscle
medicine.medical_treatment
lcsh:Medicine
030204 cardiovascular system & hematology
Biochemistry
Epithelium
Muscle
Smooth
Vascular
0302 clinical medicine
Polylactic Acid-Polyglycolic Acid Copolymer
Restenosis
Animal Cells
Cell Movement
Medicine and Health Sciences
Small interfering RNAs
lcsh:Science
Mammals
Neointimal hyperplasia
Drug Carriers
Multidisciplinary
Chemistry
Vascular endothelial cell proliferation
Drug-Eluting Stents
Animal Models
Transfection
Enzymes
Nucleic acids
Cholesterol
Experimental Organism Systems
Vertebrates
Rabbits
Cellular Types
Anatomy
Oxidoreductases
Luciferase
Research Article
Neointima
Membrane permeability
Surgical and Invasive Medical Procedures
Research and Analysis Methods
03 medical and health sciences
Genetics
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Lactic Acid
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
Cell Proliferation
RNA
Double-Stranded
Base Sequence
lcsh:R
Organisms
Biology and Life Sciences
Proteins
Endothelial Cells
Stent
Epithelial Cells
Cell Biology
medicine.disease
Gene regulation
MicroRNAs
Biological Tissue
030104 developmental biology
Stent Implantation
Amniotes
Enzymology
Cancer research
RNA
Nanoparticles
lcsh:Q
Gene expression
Polyglycolic Acid
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 3, p e0172798 (2017)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: