LncRNA H19 abrogates the protective effects of curcumin on rat carotid balloon injury via activating Wnt/β-catenin signaling pathway

Eur J Pharmacol. 2021 Nov 5:910:174485. doi: 10.1016/j.ejphar.2021.174485. Epub 2021 Sep 3.

Abstract

Intimal hyperplasia-induced restenosis is a common response to vascular endothelial damage caused by mechanical force or other stimulation, and is closely linked to vascular remodeling. Curcumin, a traditional Chinese medicine, exhibits potent protective effects in cardiovascular diseases; for example, it attenuates vascular remodeling. Although the suppressive effects of curcumin on diseases caused by vascular narrowing have been investigated, the underlying mechanisms remain unknown. Long non-coding RNAs (lncRNAs) regulate various pathological processes and affect the action of drugs. In the present study, we found that the curcumin remarkably downregulated the expression of lncRNA H19 and thereby inhibited intimal hyperplasia-induced vascular restenosis. Furthermore, the inhibition of the expression of H19 by curcumin resulted in the inactivation of the Wnt/β-catenin signaling. Overall, we show that curcumin suppresses intimal hyperplasia via the H19/Wnt/β-catenin pathway, implying that H19 is a critical molecule in the suppression of intimal hyperplasia after balloon injury by curcumin. These insights should be useful for potential application of curcumin as a therapeutic intervention in vascular stenosis.

Keywords: Carotid balloon injury; Curcumin; H19; Vascular smooth muscle cell; Wnt/β-catenin signaling.

MeSH terms

  • Animals
  • Carotid Arteries / pathology
  • Carotid Stenosis / drug therapy*
  • Carotid Stenosis / genetics
  • Carotid Stenosis / pathology
  • Cell Line
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Humans
  • Male
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Vascular Remodeling / drug effects*
  • Vascular Remodeling / genetics
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / genetics*

Substances

  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • Curcumin