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<p>Myocardial infarction (MI) causes myocardial hypoxia and subsequent cardiomyocyte death, leading to inflammatory responses that adversely affect prognosis. Clinical outcomes of MI also exhibit diurnal variation, suggesting involvement of circadian clock genes. Differentiated embryo chondrocytes 1 (DEC1) is a clock gene whose expression is induced by hypoxia and has been implicated in the regulation of apoptosis; however, its role in MI remains unclear. To investigate the function of DEC1 in MI, we established a coronary artery ligation model using wild-type and DEC1-deficient (DEC1<sup>⁻/⁻</sup>) mice. To assess the contribution of apoptosis, pifithrin-α, a p53-dependent apoptosis inhibitor, was administered following MI induction. DEC1<sup>⁻/⁻</sup> mice showed increased p53 expression and enhanced apoptosis in the infarcted myocardium. Despite increased apoptotic cell death, inflammatory cell infiltration was significantly reduced, and overall survival after MI was improved compared with wild-type mice. Administration of pifithrin-α to DEC1<sup>⁻/⁻</sup> mice attenuated apoptosis and abolished the survival benefit. Additionally, expression of survivin, an inhibitor of apoptosis protein, was downregulated in DEC1<sup>⁻/⁻</sup> hearts after MI. These findings indicate that DEC1 deficiency modulates MI outcomes by enhancing p53-dependent apoptosis while suppressing post-infarction inflammatory responses. DEC1 may therefore represent a novel regulatory factor linking hypoxia, circadian signaling, and myocardial injury.</p>

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DEC1 deficiency ameliorates myocardial ischemic injury via the p53-dependent apoptosis pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月18日

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  • Takahiro Harada,
  • Ayumu Nakashima,
  • Farina Mohamad Yusoff,
  • Naoki Ishiuchi,
  • Ki-ichiro Kawano,
  • Chiemi Sakai,
  • Mari Ishida,
  • Takayuki Yamaji,
  • Shinji Kishimoto,
  • Masato Kajikawa,
  • Tatsuya Maruhashi,
  • Masataka Nagao,
  • Shinya Takahashi,
  • Takeshi Kawamoto,
  • Yukihito Higashi

摘要

Myocardial infarction (MI) causes myocardial hypoxia and subsequent cardiomyocyte death, leading to inflammatory responses that adversely affect prognosis. Clinical outcomes of MI also exhibit diurnal variation, suggesting involvement of circadian clock genes. Differentiated embryo chondrocytes 1 (DEC1) is a clock gene whose expression is induced by hypoxia and has been implicated in the regulation of apoptosis; however, its role in MI remains unclear. To investigate the function of DEC1 in MI, we established a coronary artery ligation model using wild-type and DEC1-deficient (DEC1⁻/⁻) mice. To assess the contribution of apoptosis, pifithrin-α, a p53-dependent apoptosis inhibitor, was administered following MI induction. DEC1⁻/⁻ mice showed increased p53 expression and enhanced apoptosis in the infarcted myocardium. Despite increased apoptotic cell death, inflammatory cell infiltration was significantly reduced, and overall survival after MI was improved compared with wild-type mice. Administration of pifithrin-α to DEC1⁻/⁻ mice attenuated apoptosis and abolished the survival benefit. Additionally, expression of survivin, an inhibitor of apoptosis protein, was downregulated in DEC1⁻/⁻ hearts after MI. These findings indicate that DEC1 deficiency modulates MI outcomes by enhancing p53-dependent apoptosis while suppressing post-infarction inflammatory responses. DEC1 may therefore represent a novel regulatory factor linking hypoxia, circadian signaling, and myocardial injury.