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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:120.)
© 2007 American Heart Association, Inc.

Vascular Biology

Smoking-Induced Monocyte Dysfunction Is Reversed by Vitamin C Supplementation In Vivo

Nadina Stadler; Juliane Eggermann; Stefan Vöö; Andrea Kranz; Johannes Waltenberger

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.

Correspondence to Johannes Waltenberger, MD, PhD, FESC, Department of Cardiology, University of Maastricht, Cardiovascular Research Institute of Maastricht CARIM, P. Debyelaan 25, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands. 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.

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. 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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