Abstract 18898: Long Non-coding RNA Fingerprint Regulated by Stretch and Cyclic Strain in Vascular Smooth Muscle Cells: Implications for Aortic Aneurysms

Abstract

Background: Alterations in the characteristics of vascular smooth muscle cells (VSMCs), triggered largely by changes in mechanical stress, play a critical role in the pathophysiology of aneurysms and hypertension. Understanding the molecular determinants that link altered rheology to aberrant VSM remodeling may uncover novel approaches to treat vascular diseases. Long noncoding RNAs (lncRNAs) are a new class of noncoding RNA and emerging evidence suggest that they not only have a key role in the regulation of various biological processes but also represent a cellular hub for coordination of various cellular, inflammatory, and immune reactions involved in health and disease. In the present study, we report for the first time the lncRNA fingerprint regulated by cyclic strain in VSMCs. Methods and Results: VSMCs were plated on Bioflex plates, starved, and subjected to 20% elongation (1 Hz) for 24 h (Flexcell® FX4000™). Total RNA was extracted using TRIzol. LncRNAs and mRNAs were profiled with the Arraystar Human LncRNA Microarray V3.0. Of the 30,586 human lncRNAs screened, 580 were differentially expressed (p<0.05) in stretched VSMCs. Amongst the 26,109 protein-coding transcripts evaluated, 26 of those differentially expressed were associated with 28 of the aforementioned differentially expressed lncRNAs (p<0.05). Subsequent KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that the differentially expressed mRNAs chemokine (C-X-C motif) ligand 1/2/3/5 (CXCL1/2/3/5), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) and vascular cell adhesion protein 1 (VCAM1), were largely associated with the tumor necrosis factor (TNF) signaling pathway, which has been previously associated with VSMC stretch-response. Further Gene Ontology analysis indicated that the differentially expressed mRNAs were associated with cell differentiation, stress response, response to external stimuli and cell migration. Conclusions: We provide the first global fingerprint of cyclic strain regulated lncRNAs in VSMC cells. This information provides novel insights into the regulatory switches governing aberrant VSMC remodeling, which may have importance in the pathogenesis of aneurysms and hypertension.