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.
Highlights
Cardiovascular disease, the leading cause of death in humans, poses serious threats to life and is a heavy economic burden
Endogenous H2S is derived from the catalytic activity of two enzymes: CBS, which is expressed in the central nervous system, and CSE, which is primarily in the cardiovascular system
To determine the functional significance of H2S signaling in heart regeneration, CSE in neonatal mice was inhibited with propargylglycine (PAG)
Summary
Cardiovascular disease, the leading cause of death in humans, poses serious threats to life and is a heavy economic burden. Lineage tracing studies have found that newly generated CMs are mainly the result of division of preexisting CMs [9, 10]. For this reason, efforts have been made to identify the molecular mechanisms underlying postnatal cardiac cell cycle arrest. ROS production associated with metabolism-induced DNA damage is a major cause of cell cycle arrest [14,15,16]. How to remove these metabolic byproducts safely and effectively is a key question in myocardial regeneration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
