Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation.

Area of Science:

• Vascular Biology
• Molecular Biology
• Genomics

Background:

• Vascular smooth muscle cell (VSMC) phenotypic switching is critical in vascular pathologies.
• The role of long noncoding RNAs (lncRNAs) in VSMC biology remains largely unexplored.

Purpose of the Study:

• To investigate the role of lncRNAs in VSMC biology and pathology.
• To identify specific lncRNAs involved in VSMC phenotypic switching.

Main Methods:

• RNA sequencing to identify differentially expressed lncRNAs in human saphenous vein VSMCs stimulated with IL-1α and PDGF.
• Functional characterization of a novel lncRNA, SMILR, including knockdown experiments.
• Analysis of SMILR expression in human atherosclerotic plaques and patient plasma.

Main Results:

• Over 300 lncRNAs were identified with altered expression upon VSMC stimulation.
• A novel lncRNA, SMILR, was identified and found to be upregulated in nucleus, cytoplasm, and conditioned media post-stimulation.
• SMILR knockdown significantly reduced VSMC proliferation and altered expression of proximal genes, including HAS2.
• Increased SMILR expression was observed in unstable atherosclerotic plaques and in plasma of patients with high C-reactive protein.

Conclusions:

• SMILR is a key regulator of VSMC proliferation.
• SMILR is implicated in the pathogenesis of vascular diseases.
• Modulation of SMILR presents a potential therapeutic strategy for vascular pathologies.