Cited by 182Vitamin C and Antioxidants ResearchNitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative Stress

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Vitamin C Inhibits Endothelial Cell Apoptosis in Congestive Heart Failure

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Rössig, Lothar, Hoffmann, Jörg, Hugel, Bénédicte, Mallat, Ziad, Haase, Astrid, Freyssinet, Jean-Marie, Tedgui, Alain, Aicher, Alexandra, Zeiher, Andreas M., Dimmeler, Stefanie·2001·Circulation

DOI 10.1161/hc4301.098284

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Abstract

Background Proinflammatory cytokines like tumor necrosis factor-α and oxidative stress induce apoptotic cell death in endothelial cells (ECs). Systemic inflammation and increased oxidative stress in congestive heart failure (CHF) coincide with enhanced EC apoptosis and the development of endothelial dysfunction. Therefore, we investigated the effects of antioxidative vitamin C therapy on EC apoptosis in CHF patients. Methods and Results Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor-α and angiotensin II in vitro as assessed by DNA fragmentation, DAPI nuclear staining, and MTT viability assay. The antiapoptotic effect of vitamin C was associated with reduced cytochrome C release from mitochondria and the inhibition of caspase-9 activity. To assess EC protection by vitamin C in CHF patients, we prospectively randomized CHF patients in a double-blind trial to vitamin C treatment versus placebo. Vitamin C administration to CHF patients markedly reduced plasma levels of circulating apoptotic microparticles to 32±8% of baseline levels, whereas placebo had no effect (87±14%, P <0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients ( P <0.001). Conclusions Administration of vitamin C to CHF patients suppresses EC apoptosis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function.

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Authors: Rössig, L., Hoffmann, J., Hugel, B., Mallat, Z., Haase, A., Freyssinet, J.-M., Tedgui, A., Aicher, A., Zeiher, A. M., & Dimmeler, S.
Affiliations: From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany (L.R., J.H., A.H., A.A., A.M.Z., S.D.); INSERM U141, IFR “Circulation,” Hôpital Lariboisière, Paris, France (Z.M., A.T.); and Institut d’Hématologie et d’Immunologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France (B.H., J.-M.F.).
Goethe University Frankfurt (DE)
ORCID: Mallat, Ziad
Tedgui, Alain
Aicher, Alexandra
Zeiher, Andreas M.
Dimmeler, Stefanie
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2001-10-30
Volume: 104
Issue: 18
Pages: 2182-2187
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/hc4301.098284
OpenAlex: W2170212513
Cited by: 182
References: 29
Citations by year: 2026: 1 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 15 · 2013: 11 · 2012: 9
FWCI: 10.72
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (acceptedVersion)
Funders: Boehringer Ingelheim Fonds
Deutsche Forschungsgemeinschaft (SFB 553)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: vitamin C, congestive heart failure, endothelial cell apoptosis, endothelial dysfunction, TNF-α, angiotensin II, oxidative stress, systemic inflammation, cytochrome c release, caspase-9, antioxidant therapy
MeSH terms: Administration, Oral, Adult, Aged, Angiotensin II, Ascorbic Acid, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Drug Administration Schedule, Endothelium, Vascular, Enzyme Inhibitors, Female, Heart Failure, Humans, Injections, Intravenous, Male, Middle Aged, Prospective Studies, Tumor Necrosis Factor-alpha, Biomarkers, Apoptosis, Thiobarbituric Acid Reactive Substances, Oxidative Stress

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Vitamin C Inhibits Endothelial Cell Apoptosis in Congestive Heart Failure

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