Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation

Ballantyne, M. D. et al. (2016) Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation. Circulation, 133(21), pp. 2050-2065. (doi: 10.1161/circulationaha.115.021019) (PMID:27052414) (PMCID:PMC4872641)

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Background—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. Methods and Results—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. Conclusions—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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Garcia, Dr Raquel and McBride, Dr Martin and Dakin, Dr Rachel and McDonald, Dr Robert and Hamilton, Dr Graham and Welsh, Dr Paul and Diver, Miss Louise and MacKenzie, Dr Ruth and Sattar, Professor Naveed
Authors: Ballantyne, M. D., Pinel, K., Dakin, R., Vesey, A. T., Diver, L., MacKenzie, R., Garcia, R., Welsh, P., Sattar, N., Hamilton, G., Joshi, N., Dweck, M. R., Miano, J. M., McBride, M. W., Newby, D. E., McDonald, R. A., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Copyright Holders:Copyright © 2016 American Heart Association Inc.
First Published:First published in Circulation 133(21): 2050-2065
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
519431Interrogation and manipulation of miRNA in acute vascular injuryAndrew BakerBritish Heart Foundation (BHF)RG/09/005/27915RI CARDIOVASCULAR & MEDICAL SCIENCES