Using RNA-sequencing, researchers from the University of Glasgow identified >300 lncRNAs whose expression was altered in human saphenous vein (HSV) VSMCs following stimulation with IL1α and PDGF. They focused on a novel lncRNA (Ensembl: RP11-94A24.1) which they 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, the researchers 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, they observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein.
Localisation of SMILER
RNA FISH analysis of SMILR, cytoplasmic UBC mRNA and nuclear SNORD3 RNA in HSVSMC, Magnification x630 for all panels. UBC and SNORD3 used for confirmation of cellular compartments.
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.