Fingerprint of long non-coding RNA regulated by cyclic mechanical stretch in human aortic smooth muscle cells: implications for hypertension

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作者
Laura-Eve Mantella
Krishna K. Singh
Paul Sandhu
Crystal Kantores
Azza Ramadan
Nadiya Khyzha
Adrian Quan
Mohammed Al-Omran
Jason E. Fish
Robert P. Jankov
Subodh Verma
机构
[1] Keenan Research Centre for Biomedical Science of St. Michael’s Hospital,Division of Cardiac Surgery
[2] Keenan Research Centre for Biomedical Science of St. Michael’s Hospital,Division of Vascular Surgery
[3] University of Toronto,Department of Pharmacology & Toxicology
[4] University of Toronto,Department of Surgery
[5] University of Toronto,Institute of Medical Science
[6] University of Toronto,Laboratory Medicine and Pathobiology
[7] University of Toronto,Department of Paediatrics
[8] University of Toronto,Department of Physiology
[9] Hospital for Sick Children Research Institute,Lung Biology Programme, Physiology and Experimental Medicine
[10] University Health Network,Toronto General Research Institute
[11] University of Toronto,Heart & Stroke Richard Lewar Centre of Excellence in Cardiovascular Research
[12] King Saud University,Department of Surgery
[13] The King Saud University-Li Ka Shing Collaborative Research Program,undefined
来源
关键词
LncRNA; Vascular smooth muscle cells; Mechanical stretch;
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摘要
Emerging evidence suggests that long non-coding RNAs (lncRNAs) represent a cellular hub coordinating various cellular processes that are critical in health and disease. Mechanical stress triggers changes in vascular smooth muscle cells (VSMCs) that in turn contribute to pathophysiological changes within the vasculature. We sought to evaluate the role that lncRNAs play in mechanical stretch-induced alterations of human aortic smooth muscle cells (HASMCs). RNA (lncRNA and mRNA) samples isolated from HASMCs that had been subjected to 10 or 20% elongation (1 Hz) for 24 h were profiled with the Arraystar Human LncRNA Microarray V3.0. LncRNA expression was quantified in parallel via qRT-PCR. Of the 30,586 human lncRNAs screened, 580 were differentially expressed (DE, P < 0.05) in stretched HASMCs. Amongst the 26,109 protein-coding transcripts evaluated, 25 of those DE were associated with 25 of the aforementioned DE lncRNAs (P < 0.05). Subsequent Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DE mRNAs were largely associated with the tumor necrosis factor signaling pathway and inflammation. Gene Ontology analysis indicated that the DE mRNAs were associated with cell differentiation, stress response, and response to external stimuli. We describe the first transcriptome profile of stretch-induced changes in HASMCs and provide novel insights into the regulatory switches that may be fundamental in governing aberrant VSMC remodeling.
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页码:163 / 173
页数:10
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