title: MicroRNA-30 inhibits neointimal hyperplasia by targeting Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ).
abstract: The multifunctional Ca(2+)/calmodulin-dependent protein kinase II δ-isoform (CaMKIIδ) promotes vascular smooth muscle (VSM) proliferation, migration, and injury-induced vascular wall neointima formation. The objective of this study was to test if microRNA-30 (miR-30) family members are endogenous regulators of CaMKIIδ expression following vascular injury and whether ectopic expression of miR-30 can inhibit CaMKIIδ-dependent VSM cell function and neointimal VSM hyperplasia induced by vascular injury. The CaMKIIδ 3'UTR contains a consensus miR-30 binding sequence that is highly conserved across species. A significant decrease in miR-30 family members and increase in CaMKIIδ2 protein expression, with no change in CaMKIIδ mRNA expression, was observed in medial layers of VSM 7 days post-injury. In vitro, overexpression of miR-30c or miR-30e inhibited CaMKIIδ2 protein expression by ~50% in cultured rat aortic VSM cells, and inhibited VSM cell proliferation and migration. In vivo, lenti-viral delivery of miR-30c into injured rat carotid arteries prevented the injury-induced increase in CaMKIIδ2. Furthermore, neointima formation was dramatically inhibited by lenti-viral delivery of miR-30c in the injured medial smooth muscle. These studies define a novel mechanism for regulating CaMKIIδ expression in VSM and provide a new potential therapeutic strategy to reduce progression of vascular proliferative diseases, including atherosclerosis and restenosis.
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Yong Feng
authors.initials: YF
authors.lastname: Liu
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Amy
authors.initials: A
authors.lastname: Spinelli
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Sun
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Diane V
authors.initials: DV
authors.lastname: Singer
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Roman
authors.initials: R
authors.lastname: Ginnan
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Fatima Z
authors.initials: FZ
authors.lastname: Saddouk
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Dee
authors.initials: D
authors.lastname: Van Riper
authors.affiliation: From the Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (USA).
authors.forename: Harold A
authors.initials: HA
authors.lastname: Singer
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis*; D020212:Carotid Artery Injuries / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006965:Hyperplasia / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D051381:Rats; D017539:Tunica Intima / Q000473:pathology*
chemical_list: C556157:MIRN30 microRNA, rat; D035683:MicroRNAs; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2