title: Vitamin C inhibits endothelial cell apoptosis in congestive heart failure.
abstract: BACKGROUND
  Proinflammatory cytokines like tumor necrosis factor-alpha 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.
  
  
  RESULTS
  Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor-alpha 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.
authors.affiliation: Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Rössig
authors.forename: J
authors.initials: J
authors.lastname: Hoffmann
authors.forename: B
authors.initials: B
authors.lastname: Hugel
authors.forename: Z
authors.initials: Z
authors.lastname: Mallat
authors.forename: A
authors.initials: A
authors.lastname: Haase
authors.forename: J M
authors.initials: JM
authors.lastname: Freyssinet
authors.forename: A
authors.initials: A
authors.lastname: Tedgui
authors.forename: A
authors.initials: A
authors.lastname: Aicher
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D001205:Ascorbic Acid