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PARP1 Promotes Heart Regeneration and Cardiomyocyte Proliferation

Jiangcheng Shu1,2, Shu Yan1,2, Chenhui Ju1,2

  • 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

International Journal of Biological Sciences
|March 14, 2024
PubMed

Insights

Poly(ADP-Ribose) Polymerase 1 (PARP1) promotes heart regeneration by activating cardiomyocyte cell cycle. PARP1 may be a therapeutic target for cardiac injury.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Regenerative Medicine

Background:

  • Myocardial infarction leads to cardiomyocyte loss and impaired heart repair, often resulting in heart failure.
  • Limited cardiomyocyte proliferation after birth hinders the heart's natural regenerative capacity.

Purpose of the Study:

  • To investigate the role of Poly(ADP-Ribose) Polymerase 1 (PARP1) in regulating cardiomyocyte proliferation and heart regeneration.
  • To elucidate the molecular mechanisms by which PARP1 influences cardiac repair.

Main Methods:

  • Utilized a PARP1 knockout mouse model and PARP1 overexpression studies.
  • Employed apical resection surgery in mice to assess heart regeneration.
  • Investigated protein interactions and enzymatic activity using biochemical assays.

Main Results:

  • PARP1 knockout impaired cardiomyocyte proliferation, cardiac function, and increased scar formation.
  • PARP1 overexpression enhanced heart regeneration following apical resection.
  • PARP1 was found to interact with and poly(ADP-ribosyl)ate Heat Shock Protein 90 Alpha Family Class B Member 1 (HSP90AB1), promoting its binding with Cell Division Cycle 37 (CDC37) and activating cell cycle kinase activity.

Conclusions:

  • PARP1 plays a crucial role in promoting heart regeneration and cardiomyocyte proliferation.
  • PARP1 activates the cardiomyocyte cell cycle through the poly(ADP-ribosyl)ation of HSP90AB1.
  • PARP1 represents a potential therapeutic target for treating cardiac injury and improving heart repair.

Keywords:
PARP1cardiomyocyte proliferationcell cyclecell signalingheart regeneration

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