JACC: Basic to Translational Science (Sep 2022)

LncRNA-ZFAS1 Promotes Myocardial Ischemia-Reperfusion Injury Through DNA Methylation-Mediated Notch1 Down-Regulation in Mice

  • Mengmeng Li, BE,
  • Lei Jiao, PhD,
  • Yingchun Shao, BE,
  • Haodong Li, BS,
  • Lihua Sun, PhD,
  • Qi Yu, MM,
  • Manyu Gong, BE,
  • Dongping Liu, BS,
  • Yanying Wang, M.M,
  • Lina Xuan, PhD,
  • Xuewen Yang, MM,
  • Yunmeng Qu, BS,
  • Yaqi Wang, BS,
  • Lintong Jiang, BS,
  • Jingjing Han, BS,
  • Ying Zhang, PhD,
  • Yong Zhang, PhD

Journal volume & issue
Vol. 7, no. 9
pp. 880 – 895

Abstract

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Summary: The most devastating and catastrophic deterioration of myocardial ischemia-reperfusion injury (MIRI) is cardiomyocyte death. Here we aimed to evaluate the role of lncRNA-ZFAS1 in MIRI and delineate its mechanism of action. The level of lncRNA-ZFAS1 was elevated in MIRI hearts, and artificial knockdown of lncRNA-ZFAS1 in mice improved cardiac function. Notch1 is a potential target of lncRNA-ZFAS1, and lncRNA-ZFAS1 could bind to the promoter region of Notch1 and recruit DNMT3b to induce Notch1 methylation. Nicotinamide mononucleotide could promote the expression of Notch1 by competitively inhibiting the expression of DNMT3b and improving the apoptosis of cardiomyocytes and cardiac function.

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