title: Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation.
abstract: Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology.
  
  
  
  Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (Ensembl: RP11-94A24.1), which we termed smooth muscle-induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein.
  
  
  
  These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Margaret D
authors.initials: MD
authors.lastname: Ballantyne
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Karine
authors.initials: K
authors.lastname: Pinel
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Rachel
authors.initials: R
authors.lastname: Dakin
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Alex T
authors.initials: AT
authors.lastname: Vesey
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Louise
authors.initials: L
authors.lastname: Diver
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Ruth
authors.initials: R
authors.lastname: Mackenzie
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Raquel
authors.initials: R
authors.lastname: Garcia
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Graham
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Nikhil
authors.initials: N
authors.lastname: Joshi
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Miano
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.).
authors.forename: Robert A
authors.initials: RA
authors.lastname: McDonald
authors.affiliation: From BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.D.B., R.D., L.D., R.M., R.G., P.W., N.S., M.W.N., R.A.M., A.H.B.); British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, Edinburgh, United Kingdom (M.D.B., K.P., A.T.V., N.J., M.R.D., D.E.N., R.A.M., A.H.B.); Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, The University of Glasgow, United Kingdom (G.H.); and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (J.M.M.). andrew.h.baker@glasgow.ac.uk.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D029742:Caenorhabditis elegans Proteins; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000502:physiology*; D012501:Saphenous Vein / Q000166:cytology / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D062085:RNA, Long Noncoding
keywords: RNA, untranslated; atherosclerosis; cell proliferation; microRNAs; plasma protein, human