title: Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization.
abstract: The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA. In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells. This analysis was performed using cardiovascular disease-focused miRNA arrays in both mouse and human cells. The potential clinical importance of actin polymerization in aortic aneurysm was evaluated using biopsies from mildly dilated human thoracic aorta in patients with stenotic tricuspid or bicuspid aortic valve. By integrating information from multiple qPCR based miRNA arrays we identified a group of five miRNAs (miR-1, miR-22, miR-143, miR-145 and miR-378a) that were sensitive to actin polymerization and MRTF-A overexpression in both mouse and human vascular smooth muscle. With the exception of miR-22, these miRNAs were also relatively enriched in striated and/or smooth muscle containing tissues. Actin polymerization was found to be dramatically reduced in the aorta from patients with mild aortic dilations. This was associated with a decrease in actin/MRTF-regulated miRNAs. In conclusion, the transcriptional co-activator MRTF-A and actin polymerization regulated a subset of miRNAs in vascular smooth muscle. Identification of novel miRNAs regulated by actin/MRTF-A may provide further insight into the mechanisms underlying vascular disease states, such as aortic aneurysm, as well as novel ideas regarding therapeutic strategies. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Azra
authors.initials: A
authors.lastname: Alajbegovic
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Karolina M
authors.initials: KM
authors.lastname: Turczyńska
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Tran Thi
authors.initials: TT
authors.lastname: Hien
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Cidad
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swärd
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hellstrand
authors.affiliation: Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Della Corte
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Forte
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: sebastian.albinsson@med.lu.se.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D058105:Polymerization; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D000199:Actins; D035683:MicroRNAs; C511173:Mrtfa protein, mouse; D015534:Trans-Activators
keywords: Actin polymerization; MRTF-A; MicroRNA; Phenotype; Smooth muscle; Vascular disease