title: Smoking-induced monocyte dysfunction is reversed by vitamin C supplementation in vivo.
abstract: OBJECTIVE
  The role of antioxidants in preventing vascular disease remains controversial. Vascular endothelial growth factor (VEGF-A) is important for endothelial and monocyte function. This study investigated the negative effects of smoking on monocyte migratory responsiveness to VEGF-A and the usefulness of vitamin C to prevent smoking-induced monocyte dysfunction.
  
  
  RESULTS
  The chemotactic response of isolated monocytes from a cohort of 17 non-smokers and 10 smokers toward VEGF-A was assessed. VEGF-A significantly stimulated the migration of monocytes in non-smokers; the monocytes from smokers failed to respond to VEGF-A. Repeated analysis after 2 weeks of vitamin C intake (2 g/d) showed a fully restored VEGF-A-induced monocyte migration in smokers. VEGF-A serum levels were not altered by vitamin C. VEGF-A-inducible kinase activity was intact in monocytes from smokers as assessed by in vitro kinase assay. Monocyte dysfunction can be mimicked in vitro by challenging monocytes with a range of reactive oxygen species (ROS).
  
  
  CONCLUSIONS
  Stimulation of monocyte migration by VEGF-A was severely attenuated in smokers, and the deficit observed was surmounted by vitamin C supplementation. The negative effects of smoking on monocyte function may translate into adverse impacts on VEGF-A-dependent repair processes such as arteriogenesis. These results propose a causative role of oxidative stress in smoking-induced monocyte dysfunction.
authors.affiliation: Department of Cardiology, University of Maastricht, Cardiovascular Research Institute of Maastricht, P. Debyelaan 25, NL-6202 AZ Maastricht, The Netherlands.
authors.forename: Nadina
authors.initials: N
authors.lastname: Stadler
authors.forename: Juliane
authors.initials: J
authors.lastname: Eggermann
authors.forename: Stefan
authors.initials: S
authors.lastname: Vöö
authors.forename: Andrea
authors.initials: A
authors.lastname: Kranz
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D019587:Dietary Supplements; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D001205:Ascorbic Acid