title: Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells.
abstract: The molecular mechanisms responsible for sepsis-induced endothelial dysfunction leading to an elevated risk of cardiovascular diseases remain undefined. Endotoxic or septic shock is a potentially lethal complication of systemic infection by Gram-negative bacteria. Lipopolysaccharide (LPS) is a critical glycolipid component of the outer wall of Gram-negative bacteria, and many of the sepsis-associated cellular signals by Gram-negative bacteria are attributed to LPS. Given that LPS has an established role in the pathophysiology of sepsis and long non-coding RNAs (lncRNAs) have been reported to critically regulate vascular homeostasis, a systematic transcriptional survey was conducted to evaluate the impact of LPS stimulation on human endothelial lncRNAs and protein-coding transcripts (mRNAs). LncRNAs and mRNAs from LPS-treated (100 ng/mL; 24 h) human umbilical vein endothelial cells (HUVECs) were profiled with the Arraystar Human lncRNA Expression Microarray V3.0. Of the 30,584 lncRNAs screened, 871 were significantly upregulated and 1068 significantly downregulated (p < 0.05) in response to LPS. In the same HUVEC samples, 733 of the 26,106 mRNAs screened were upregulated and 536 were downregulated. Among the differentially expressed lncRNAs, AL132709.5 was the most upregulated (~70 fold) and CTC-459I6.1 the most downregulated (~28 fold). Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in cytokine-cytokine receptor interaction, infectious diseases, TNF signaling pathway, FoxO signaling pathway, and pathways in cancer. This is the first lncRNA and mRNA transcriptome profile of LPS-mediated changes in human endothelial cells. These observations may reveal novel endothelial targets of LPS that may be involved in the vascular pathology of sepsis.
authors: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. singhk@smh.ca.|Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. singhk@smh.ca.|Department of Surgery, University of Toronto, Toronto, ON, Canada. singhk@smh.ca.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada. singhk@smh.ca.
authors: Krishna K
authors: KK
authors: Singh
authors: Division of Cardiology, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors: Pratiek N
authors: PN
authors: Matkar
authors: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
authors: Shoaib
authors: S
authors: Muhammad
authors: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
authors: Adrian
authors: A
authors: Quan
authors: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
authors: Vijay
authors: V
authors: Gupta
authors: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.|Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
authors: Hwee
authors: H
authors: Teoh
authors: Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.|Department of Surgery, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|King Saud University-Li Ka Shing Collaborative Research Program, Department of Surgery, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors: Mohammed
authors: M
authors: Al-Omran
authors: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. vermasu@smh.ca.|Department of Surgery, University of Toronto, Toronto, ON, Canada. vermasu@smh.ca.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada. vermasu@smh.ca.
authors: Subodh
authors: S
authors: Verma
mesh_terms: D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D062085:RNA, Long Noncoding / Q000096:biosynthesis*
chemical_list: D008070:Lipopolysaccharides; D062085:RNA, Long Noncoding
keywords: Endothelial cells; LPS; lncRNA