title: MicroRNA-217 suppresses homocysteine-induced proliferation and migration of vascular smooth muscle cells via N-methyl-D-aspartic acid receptor inhibition.
abstract: Hyperhomocysteine has become a critical risk for atherosclerosis and can stimulate proliferation and migration of vascular smooth muscle cells (VSMCs). N-methyl-D-aspartic acid receptor (NMDAR) is a receptor of homocysteine and mediates the effects of homocysteine on VSMCs. Bioinformatics analysis has shown NMDAR is a potential target of microRNA-217 (miR-217), which exerts multiple functions in cancer tumorigenesis and carotid plaque progression. In this study, we sought to investigate the role of miR-217 in VSMCs phenotype transition under homocysteine exposure and elucidate its effect on atherosclerotic plaque formation. After treating with several doses of homocysteine (0-8 × 10(-4)  mol/L) for 24 hours, the expression of miR-217 in HA-VSMCs and rat aortic VSMCs was not altered. Intriguingly, the expression of NMDAR mRNA and protein was reduced by homocysteine in a dose-dependent manner. Transfection of miR-217 mimic significantly inhibited the proliferation and migration of VSMCs with homocysteine treatment, while transfection of miR-217 inhibitor promoted VSMCs migration. Moreover, miR-217 mimic down-regulated while miR-217 inhibitor up-regulated NMDAR protein expression but not NMDAR mRNA expression. Through luciferase reporter assay, we showed that miR-217 could directly bind to the 3'-UTR of NMDAR. MiR-217 mimic transfection also released the inhibition of cAMP-response element-binding protein (CREB)-PGC-1α signalling induced by homocysteine. Additionally, restoration of PGC-1α expression via AdPGC-1α infection markedly suppressed VSMCs proliferation through the degradation of NADPH oxidase (NOX1) and reduction of reactive oxygen species (ROS). Collectively, our study identified the role of miR-217 in regulating VSMCs proliferation and migration, which might serve as a target for atherosclerosis therapy.
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qian
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Shanling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*
chemical_list: C553315:MIRN217 microRNA, human; D035683:MicroRNAs; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine
keywords: N-methyl-D-aspartic acid receptor; atherosclerosis; homocysteine; microRNA-217; vascular smooth muscle cells