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Sirt4 Deficiency Promotes Cardiomyocyte Proliferation and Cardiac Repair

Weijing Liu1,2, Jie Feng1,3, Yuan Zhang4

  • 1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Journal of Cellular and Molecular Medicine
|August 22, 2025
PubMed

Insights

Sirt4 protein inhibits heart regeneration by damaging DNA and stopping cardiomyocyte proliferation. Sirt4 deficiency promotes heart repair and improves function after injury, suggesting Sirt4 inhibition as a potential therapy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Regenerative Medicine

Background:

  • Mammalian hearts have limited regenerative capacity post-birth.
  • Cardiomyocyte cell cycle exit limits cardiac repair.
  • The role of sirtuins in cardiomyocyte proliferation is largely unknown.

Purpose of the Study:

  • Investigate the role of Sirt4 in cardiomyocyte proliferation.
  • Determine Sirt4's impact on cardiac regeneration and repair.
  • Evaluate Sirt4 as a therapeutic target for heart disease.

Main Methods:

  • Assessed Sirt4 expression during heart development.
  • Utilized in vitro and in vivo models with Sirt4 overexpression.
  • Examined Sirt4-knockout mice and adult mice subjected to ischemia-reperfusion injury.

Main Results:

  • Sirt4 overexpression inhibited cardiomyocyte proliferation and neonatal heart regeneration.
  • Sirt4 deficiency enhanced cardiomyocyte proliferation and extended the regeneration window.
  • Sirt4 knockout improved cardiac function and reduced fibrosis post-injury.

Conclusions:

  • Sirt4 is a key regulator of cardiomyocyte proliferation and cardiac repair.
  • Targeting Sirt4 inhibition offers a potential therapeutic strategy for ischemic heart diseases.
  • Modulating Sirt4 could enhance cardiac regenerative capacity.

Keywords:
Sirt4cardiomyocyte proliferationheart regenerationoxidative DNA damage

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