title: 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.
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Bae
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Yejin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Seoul National University Hospital, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Seoul National University Hospital, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Lee
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea. Electronic address: genius29@snu.ac.kr.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea. Electronic address: kinglee@snu.ac.kr.
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000235:genetics / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis*; D015536:Down-Regulation; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000503:physiopathology; D015151:Immunoblotting; D008661:Metabolism, Inborn Errors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D002395:Catecholamines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001205:Ascorbic Acid
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