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Hydrogen Sulfide Promotes Cardiomyocyte Proliferation and Heart Regeneration via ROS Scavenging
Jianqiu Pei1, Fang Wang1, Shengqiang Pei1
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Abstract:
Neonatal mouse hearts can regenerate completely in 21 days after cardiac injury, providing an ideal model to exploring heart regenerative therapeutic targets. The oxidative damage by Reactive Oxygen Species (ROS) is one of the critical reasons for the cell cycle arrest of cardiomyocytes (CMs), which cause mouse hearts losing the capacity to regenerate in 7 days or shorter after birth. As an antioxidant, hydrogen sulfide (H2S) plays a protective role in a variety of diseases by scavenging ROS produced during the pathological processes. In this study, we found that blocking H2S synthesis by PAG (H2S synthase inhibitor) suspended heart regeneration and CM proliferation with ROS deposition increase after cardiac injury (myocardial infarction or apex resection) in 2-day-old mice. NaHS (a H2S donor) administration improved heart regeneration with CM proliferation and ROS elimination after myocardial infarction in 7-day-old mice. NaHS protected primary neonatal mouse CMs from H2O2-induced apoptosis and promoted CM proliferation via SOD2-dependent ROS scavenging. The oxidative DNA damage in CMs was reduced with the elimination of ROS by H2S. Our results demonstrated for the first time that H2S promotes heart regeneration and identified NaHS as a potent modulator for cardiac repair.
Insights
Hydrogen sulfide (H2S) promotes neonatal mouse heart regeneration by scavenging reactive oxygen species (ROS). This study identifies hydrogen sulfide as a potential therapeutic target for cardiac repair and improving heart regeneration.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Oxidative Stress Research
Background:
- Neonatal mouse hearts exhibit remarkable regenerative capacity, offering a model for studying cardiac repair.
- Reactive Oxygen Species (ROS) induce cardiomyocyte cell cycle arrest, impairing heart regeneration in neonatal mice.
- Hydrogen sulfide (H2S), an antioxidant, mitigates ROS and protects against cellular damage in various diseases.
Purpose of the Study:
- To investigate the role of H2S in neonatal mouse heart regeneration.
- To determine if H2S can overcome ROS-induced inhibition of cardiac repair.
- To identify H2S-based therapeutic strategies for promoting heart regeneration.
Main Methods:
- Cardiac injury models (myocardial infarction, apex resection) in neonatal mice.
- Inhibition of H2S synthesis using DL-propargylglycine (PAG).
- Administration of a hydrogen sulfide donor, NaHS.
- Assessment of cardiomyocyte proliferation, ROS levels, and oxidative DNA damage.
- In vitro studies using primary neonatal mouse cardiomyocytes exposed to hydrogen peroxide (H2O2).
Main Results:
- Inhibiting H2S synthesis with PAG halted heart regeneration and cardiomyocyte proliferation post-injury, accompanied by increased ROS.
- NaHS administration enhanced heart regeneration and cardiomyocyte proliferation after myocardial infarction, reducing ROS.
- NaHS protected cardiomyocytes from H2O2-induced apoptosis and promoted proliferation via SOD2-dependent ROS scavenging.
- H2S treatment decreased oxidative DNA damage in cardiomyocytes by eliminating ROS.
Conclusions:
- Hydrogen sulfide (H2S) is crucial for neonatal mouse heart regeneration.
- H2S promotes cardiac repair by scavenging ROS and protecting cardiomyocytes from oxidative stress and apoptosis.
- NaHS is a promising therapeutic agent for enhancing cardiac regeneration.
