Vitamin C prevents stress-induced damage on the heart caused by the death of cardiomyocytes, through down-regulation of the excessive production of catecholamine, TNF-α, and ROS production in Gulo(-/-)Vit C-Insufficient mice

Abstract

It is thought that vitamin C has protective roles on stress-induced heart damage and the development of cardiovascular diseases, but its precise role and mechanisms are unclear. In the present study, we investigated the specific mechanisms by which vitamin C leads to protecting the heart from stress-induced damage in the Gulo(-/-) mice which cannot synthesize vitamin C like humans. By exposure to stress (1h/day), the heartbeat and cardiac output in vitamin C-insufficient Gulo(-/-) mice were definitely decreased, despite a significant increase of adrenaline (ADR) and noradrenaline (NA) production. A change of cardiac structure caused by the death of cardiomyocytes and an increased expression of matrix metalloprotease (MMP)-2 and -9 were also found. Moreover, lipid peroxidation and the production of tumor necrosis factor-alpha (TNF-α) in the heart were increased. Finally, all vitamin C-insufficient Gulo(-/-) mice were expired within 2 weeks. Interestingly, all of the findings in vitamin C-insufficient Gulo(-/-) mice were completely prevented by the supplementation of a sufficient amount of vitamin C. Taken together, vitamin C insufficiency increases the risk of stress-induced cardiac damage with structural and functional changes arising from the apoptosis of cardiomyocytes.

Keywords: ADR; ANF; EF; FS; G-protein coupled receptor kinase; GRK; GSH; Gulo(−/−) mice; Heart injury; IL; MDA; MMP; MnSOD; N-acetyl-L-cysteine; NA; NAC; NADPH; ROS; Stress; TNF-α; Vitamin C insufficiency; adrenaline; atrial natriuretic factor; ejection fraction; fractional shortening; glutathione; interleukin; malondialdehyde; manganese superoxide dismutase; matrix metalloproteinase; nicotinamide adenine dinucleotide phosphate; noradrenaline; reactive oxygen species; tumor necrosis factor-alpha.