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LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling.

Publication ,  Journal Article
Simion, V; Zhou, H; Pierce, JB; Yang, D; Haemmig, S; Tesmenitsky, Y; Sukhova, G; Stone, PH; Libby, P; Feinberg, MW
Published in: JCI insight
November 2020

Long noncoding RNAs (lncRNAs) play important roles in regulating diverse cellular processes in the vessel wall, including atherosclerosis. RNA-Seq profiling of intimal lesions revealed a lncRNA, VINAS (Vascular INflammation and Atherosclerosis lncRNA Sequence), that is enriched in the aortic intima and regulates vascular inflammation. Aortic intimal expression of VINAS fell with atherosclerotic progression and rose with regression. VINAS knockdown reduced atherosclerotic lesion formation by 55% in LDL receptor-deficient (LDLR-/-) mice, independent of effects on circulating lipids, by decreasing inflammation in the vessel wall. Loss- and gain-of-function studies in vitro demonstrated that VINAS serves as a critical regulator of inflammation by modulating NF-κB and MAPK signaling pathways. VINAS knockdown decreased the expression of key inflammatory markers, such as MCP-1, TNF-α, IL-1β, and COX-2, in endothelial cells (ECs), vascular smooth muscle cells, and bone marrow-derived macrophages. Moreover, VINAS silencing decreased expression of leukocyte adhesion molecules VCAM-1, E-selectin, and ICAM-1 and reduced monocyte adhesion to ECs. DEP domain containing 4 (DEPDC4), an evolutionary conserved human ortholog of VINAS with approximately 74% homology, showed similar regulation in human and pig atherosclerotic specimens. DEPDC4 knockdown replicated antiinflammatory effects of VINAS in human ECs. These findings reveal a potentially novel lncRNA that regulates vascular inflammation, with broad implications for vascular diseases.

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Published In

JCI insight

DOI

EISSN

2379-3708

ISSN

2379-3708

Publication Date

November 2020

Volume

5

Issue

21

Start / End Page

140627

Related Subject Headings

  • Swine
  • Signal Transduction
  • Receptors, LDL
  • RNA, Long Noncoding
  • NF-kappa B
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice
  • Male
  • Macrophages
 

Citation

APA
Chicago
ICMJE
MLA
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Simion, V., Zhou, H., Pierce, J. B., Yang, D., Haemmig, S., Tesmenitsky, Y., … Feinberg, M. W. (2020). LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling. JCI Insight, 5(21), 140627. https://doi.org/10.1172/jci.insight.140627
Simion, Viorel, Haoyang Zhou, Jacob B. Pierce, Dafeng Yang, Stefan Haemmig, Yevgenia Tesmenitsky, Galina Sukhova, Peter H. Stone, Peter Libby, and Mark W. Feinberg. “LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling.JCI Insight 5, no. 21 (November 2020): 140627. https://doi.org/10.1172/jci.insight.140627.
Simion V, Zhou H, Pierce JB, Yang D, Haemmig S, Tesmenitsky Y, et al. LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling. JCI insight. 2020 Nov;5(21):140627.
Simion, Viorel, et al. “LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling.JCI Insight, vol. 5, no. 21, Nov. 2020, p. 140627. Epmc, doi:10.1172/jci.insight.140627.
Simion V, Zhou H, Pierce JB, Yang D, Haemmig S, Tesmenitsky Y, Sukhova G, Stone PH, Libby P, Feinberg MW. LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling. JCI insight. 2020 Nov;5(21):140627.

Published In

JCI insight

DOI

EISSN

2379-3708

ISSN

2379-3708

Publication Date

November 2020

Volume

5

Issue

21

Start / End Page

140627

Related Subject Headings

  • Swine
  • Signal Transduction
  • Receptors, LDL
  • RNA, Long Noncoding
  • NF-kappa B
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice
  • Male
  • Macrophages