P42: Nitrite exposure under hypoxia improve heart regeneration in zebrafish

Abstract

Myocardial infarction is a leading cause of death in developed countries. It is now apparent that nitrite has remarkable cytoprotective and anti-apoptotic effects on the cardiac muscle cells following injury. Reduction of nitrite to nitric oxide during ischemia protects the heart against injury from ischemia/reperfusion by reducing apoptosis and necrosis at the infarct site. Yet in mammals there is little or no significant cardiac muscle regeneration after an injury such as acute myocardial infarction and the scar persists throughout the entire adult life. In contrast adult zebrafish possess a remarkable ability to replace damaged or lost tissue after injury, providing a model for understanding heart regeneration. After resection or cryoinjury of the ventricular apex, pre-existing cardiomyocytes re-enter the cell cycle to generate new cardiac muscle. We investigated the effects of hypoxia and nitrite on zebrafish heart regeneration and found that low concentrations (10 μM) of nitrite reduced scar tissue at 5 and 10 days post cryoinjury. Exposure to nitrite under normoxia or to hypoxia alone had no positive effects on regeneration. However simultaneous exposure to nitrite and hypoxia resulted in an increase of cell proliferation showing a positive interaction of hypoxia and nitrite. A specific increase in proliferating cardiomyocytes is detectable at 5 days after cryoinjury and amputation. These studies show that physiological levels of nitrite improve cardiomyocyte proliferation and cardiac regeneration following cardiac injury in the zebrafish. Nothing to disclose.