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

Free Radic Biol Med. 2013 Dec:65:573-583. doi: 10.1016/j.freeradbiomed.2013.07.023. Epub 2013 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / genetics
  • Ascorbic Acid / metabolism*
  • Catecholamines / biosynthesis*
  • Down-Regulation
  • Echocardiography
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Heart / physiopathology
  • Immunoblotting
  • Metabolism, Inborn Errors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism*
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Catecholamines
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Ascorbic Acid

Supplementary concepts

  • L-Gulonolactone Oxidase, Nonfunctional