Smooth Muscle Enriched Long Noncoding RNA ( SMILR ) Regulates Cell Proliferation
Open accessAbstract
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.
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Non-coding RNAs also control VSMC plasticity, evidenced by the effect of specific miRNAs and long non-coding RNAs on VSMC biology and function.
“Non-coding RNAs also control VSMC plasticity 235,236 evidenced by the effect of specific miRNAs and long non-coding RNAs on VSMC biology and function 237,238 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [238]
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Research works printed but not linked: 2
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Self-citation
- 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., & Baker, A. H.
- Affiliations
- University of Rochester Medicine (US)
- 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...
- Corresponding author
- Baker, Andrew H.
- ORCID
- Venue
- Circulation
- Published
- 2016-05-24
- Volume
- 133
- Issue
- 21
- Pages
- 2050-2065
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4872641
- OpenAlex
- W2315863900
- Cited by
- 223
- References
- 59
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 19 · 2023: 15 · 2022: 23 · 2021: 24 · 2020: 32 · 2019: 32 · 2018: 37 · 2017: 13 · 2016: 6
- FWCI
- 17.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Circulation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- UCrea (University of Cantabria) (submittedVersion, cc-by)
- Funders
- Wellcome Trust
- NHS Health Scotland
- British Heart Foundation (FS/12/66/30003, FS/13/77/30488, RG/09/005/27915, FS/14/78/31020, PG/12/8/29371, RG/14/3/30706)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- long non-coding RNA, vascular smooth muscle cells, cell proliferation, phenotypic switching, atherosclerosis, plaque vulnerability, interleukin-1 alpha, platelet-derived growth factor, HAS2, C-reactive protein, intimal hyperplasia
- MeSH terms
- Cells, Cultured, Humans, Muscle, Smooth, Vascular, Saphenous Vein, Caenorhabditis elegans Proteins, Myocytes, Smooth Muscle, Cell Proliferation, Gene Knockdown Techniques, RNA, Long Noncoding
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