Smooth Muscle Enriched Long Non-Coding RNA (SMILR) Regulates Cell Proliferation
Background—Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state is implicated in diverse vascular pathologies including atherogenesis, plaque stabilisation, and neointimal hyperplasia. However, very little is known as to the role of long non coding RNA (lncRNA) during this process. Here we investigated a role for long non-coding (lnc)RNAs in VSMC biology and pathology.
Methods and Results—Using RNA-sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein (HSV) VSMCs following stimulation with IL1α and PDGF. 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 were also altered by IL1α/PDGF 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 VSMC proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.
- Received December 22, 2015.
- Revision received March 15, 2016.
- Accepted March 28, 2016.
Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.