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 |
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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 |
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