on October 19, 2006
Published online before print October 19, 2006, doi: 10.1161/01.ATV.0000250614.97896.4c
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Submitted on March 18, 2006
Accepted on October 5, 2006
Smoking-Induced Monocyte Dysfunction Is Reversed by Vitamin C Supplementation In Vivo
Nadina Stadler ;
From the Department of Cardiology (N.S., S.V., J.W.), University of Maastricht, Cardiovascular Research Institute of Maastricht (CARIM), The Netherlands; and the Department of Internal Medicine II (J.E., A.K., J.W.), Ulm University Medical Center, Ulm, Germany.
* To whom correspondence should be addressed. E-mail: j.waltenberger{at}cardio.azm.nl.
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.
Methods and 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 (2g/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.
Key words: smoking • monocyte dysfunction • free radicals • antioxidants • growth factors
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