The role of long noncoding RNA Nron in atherosclerosis development and plaque stability

Meng Du, Cheng Wang, Liuye Yang, Bing Liu, Zhe Zheng, Liu Yang, Fengxiao Zhang, Jiangtong Peng, Dan Huang, Kai Huang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The major clinical consequences of atherosclerosis such as myocardial infarction or stroke are because of thrombotic events associated with acute rupture or erosion of an unstable plaque. Here, we identify an lncRNA Noncoding Repressor of NFAT (Nron) as a critical regulator of atherosclerotic plaque stability. Nron overexpression (OE) in vascular smooth muscle cells (VSMC) induces a highly characteristic architecture of more-vulnerable plaques, while Nron knockdown (KD) suppresses the development of atherosclerosis and favors plaque stability. Mechanistically, Nron specifically binds to and negatively regulates NFATc3, thus inhibiting the proliferation and promoting the apoptosis of VSMCs. Moreover, we also provide evidence that Nron increases the production and secretion of VEGFA from VSMCs, which functions as a paracrine factor to enhance intra-plaque angiogenesis. All of these effects contribute to plaque instability. Genetic or pharmacological inhibition of Nron may have potential for future therapy of atherosclerosis.

Original languageEnglish (US)
Article number103978
JournaliScience
Volume25
Issue number3
DOIs
StatePublished - Mar 18 2022
Externally publishedYes

Keywords

  • Functional aspects of cell biology
  • Molecular biology
  • Pathophysiology

ASJC Scopus subject areas

  • General

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