LncRNA GAS5 regulates vascular smooth muscle cell cycle arrest and apoptosis via p53 pathway

Rui Tang, Xiaohan Mei, Yung Chun Wang, Xiao Bing Cui, Gui Zhang, Wenjing Li, Shi You Chen

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Vascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) are a class of gene regulators functioning through various mechanisms in physiological and pathological conditions. By using cultured VSMC and rat carotid artery balloon injury model, we found that lncRNA growth arrest specific 5 (GAS5) serves as a negative regulator for VSMC survival in vascular remodeling. By manipulating GAS5 expression via adenoviral overexpression or short hairpin RNA knockdown, we found that GAS5 suppresses VSMC proliferation while promoting cell cycle arrest and inducing cell apoptosis. Mechanistically, GAS5 directly binds to p53 and p300, stabilizes p53-p300 interaction, and thus regulates VSMC cell survival via induction of p53-downstream target genes. Importantly, local delivery of GAS5 via adenoviral vector suppresses balloon injury-induced neointima formation along with an increased expression of p53 and apoptosis in neointimal SMCs. Our study demonstrated for the first time that GAS5 negatively impacts VSMC survival via activation the p53 pathway during vascular remodeling.

Original languageEnglish
Pages (from-to)2516-2525
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1865
Issue number9
DOIs
StatePublished - Sep 1 2019

Keywords

  • GAS5
  • LncRNA
  • p53
  • Smooth muscle cell
  • Vascular remodeling

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