The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-βR1 signalling pathway

J Cell Physiol. 2021 Mar;236(3):2058-2069. doi: 10.1002/jcp.29993. Epub 2020 Aug 11.


The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein-1 and interleukin-10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL-mediated inhibition of let-7b regulates HUVEC dysfunction by targeting the TGF-βR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.

Keywords: ANRIL; coronary artery disease; endothelial dysfunction; inflammatory; let-7b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / genetics
  • Base Sequence
  • Biomarkers / metabolism
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / pathology*
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • MicroRNAs / metabolism*
  • Models, Biological
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type I / metabolism*
  • Signal Transduction* / genetics
  • Smad Proteins / metabolism
  • Up-Regulation / genetics


  • Biomarkers
  • CDKN2B antisense RNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • Smad Proteins
  • mirnlet7 microRNA, human
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human