ZFIN ID: ZDB-PUB-191115-4
Nitrite improves heart regeneration in zebrafish
Rochon, E., Missinato, M.A., Xue, J., Tejero, J., Tsang, M., Gladwin, M.T., Corti, P.
Date: 2019
Source: Antioxidants & redox signaling   32(6): 363-377 (Journal)
Registered Authors: Tsang, Michael
Keywords: none
MeSH Terms:
  • Animals
  • Cell Proliferation/physiology
  • Heart/physiology*
  • Myocytes, Cardiac/metabolism
  • Nitrites/metabolism*
  • Regeneration/physiology*
  • Wound Healing/physiology
  • Zebrafish/physiology*
PubMed: 31724431 Full text @ Antioxid. Redox Signal.
Nitrite is reduced to nitric oxide (NO) under physiological and pathological hypoxic conditions, modulates angiogenesis and improves ischemia-reperfusion injury. While adult mammals lack the ability to regenerate the heart after injury, this is preserved in the neonates and efforts to reactivate this process are of great interest. Unlike mammals, the adult zebrafish maintain the innate ability to regenerate their hearts following injury, providing an important model to study cardiac regeneration. We thus explored the effects of physiological levels of nitrite on cardiac and fin regeneration and down-stream cellular and molecular signaling pathways in response to amputation and cryoinjury.
Nitrite treatment of zebrafish after amputation or cryoinjury to the heart in hypoxic water (~3ppm of oxygen) increases cardiomyocyte proliferation, improves angiogenesis and enhances early recruitment of thrombocytes, macrophages and neutrophils to the injury. When tested in a fin regeneration model, allowing for inhibition of NO signaling with cPTIO, the nitrite-dependent increase in neutrophil recruitment was found to be dependent on NO.
This is the first study to evaluate effects of physiological levels of nitrite on cardiac regeneration in response to cardiac injury, with the observation that nitrite in water accelerates zebrafish heart regeneration.
Physiological and therapeutic levels of nitrite increase thrombocytes, neutrophils and macrophages recruitment to the heart after amputation and cryoinjury in zebrafish, resulting in accelerated cardiomyocyte proliferation and angiogenesis. Translation of this finding to mammalian models of injury in early development may provide an opportunity to improve outcomes during intrauterine fetal or neonatal cardiac surgery.