Hydrogen Sulfide Promotes Postnatal Cardiomyocyte Proliferation by Upregulating SIRT1 Signaling Pathway

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Developmental Biology

Background:

• Hydrogen sulfide (H₂S) is recognized as a gasotransmitter and antioxidant involved in mammalian physiological and pathological processes.
• The role of H₂S in regulating cardiomyocyte (CM) proliferation during postnatal development is not well understood.

Purpose of the Study:

• To investigate the function of H₂S in postnatal mouse cardiomyocyte proliferation.
• To elucidate the molecular mechanisms underlying H₂S-mediated CM proliferation.

Main Methods:

• In vitro studies using neonatal mouse primary cardiomyocytes treated with sodium hydrosulfide (NaHS).
• In vivo experiments involving exogenous H₂S administration in mice at postnatal days 7 and 14.
• Assessment of CM proliferation and total CM numbers.
• Analysis of SIRT1 protein expression and its modulation using pharmacological inhibitors (EX-527) and activators (SRT1720), as well as genetic silencing (si-SIRT1).

Main Results:

• NaHS significantly increased neonatal mouse CM proliferation in a dose-dependent manner in vitro.
• Exogenous H₂S administration promoted CM proliferation and increased total CM numbers in vivo.
• NaHS treatment upregulated SIRT1 protein expression.
• SIRT1 inhibition decreased CM proliferation, while SIRT1 activation promoted it.
• Blocking SIRT1 abrogated the proliferative effect of NaHS on CMs.

Conclusions:

• H₂S plays a significant promotional role in cardiomyocyte proliferation both in vitro and in vivo.
• SIRT1 is essential for H₂S-mediated cardiomyocyte proliferation.
• H₂S may act as a key modulator of heart development during the postnatal period.