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No evidence for prooxidative effects of homocysteine in vascular endothelial cells

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Abstract

Many epidemiological studies predict a role for homocysteine (HCys) in cardiovascular disease occurrence, progression, and risk factors. In vitro studies demonstrated that HCys is an atherogenic determinant that promotes oxidant stress, inflammation, endothelial dysfunction and cell proliferation. This study originally attempted to examine the mechanism by which exposure of endothelial cells to HCys (0–250 µM) initiates inflammatory reaction and oxidative stress, by (i) investigating whether physiological and pathophysiological concentrations of HCys exhibit a prooxidative activity in vitro, (ii) examining the interaction of monocyte adhesion (Mono Mac 6) to monolayers of human microvascular endothelial cells (HMEC-1) exposed to different HCys concentrations, and (iii) examining if adherent monocytes increase reactive oxygen species either in endothelial cells or in monocytes themselves. However, our results demonstrate that HCys had neither prooxidative nor cytotoxic effects on endothelial cells. Only a moderate time- and concentration-dependent increase in monocyte adhesion up to 28.3 ± 5.5% was achieved relative to control after 4 h of HCys stimulation. This effect was accompanied by an increased VCAM and ICAM-1 mRNA expression. This “proinflammatory” effect appeared also when HMEC-1 cells were incubated with cysteine or glutathione at the concentration range 0–250 µM, demonstrating a non-specific rather than a specific HCys effect. In addition, adherent monocytes did not increase ROS formation neither in endothelial cells nor in monocytes themselves, indicating no direct or indirect cytotoxic or prooxidative effects of HCys.

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Acknowledgment

The authors thank Dr. Gurunadh Reddy Chichili (Oklahoma Medical Research Foundation, Oklahoma, USA) for critical reading of the manuscript.

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Authors and Affiliations

  1. zet Life Science Laboratory Linz, Centre for Alternative and Complementary Methods to Animal Testing, Scharitzerstraße 6-8, 4020, Linz, Austria

    Juergen Frank

  2. Ocular Neurodegeneration Research Group, Centre for Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany

    Susanne C. Beck

  3. Dept. of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany

    Andrea Flaccus & Hans K. Biesalski

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  1. Juergen Frank
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  2. Susanne C. Beck
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  3. Andrea Flaccus
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  4. Hans K. Biesalski
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Correspondence to Juergen Frank.

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Frank, J., Beck, S.C., Flaccus, A. et al. No evidence for prooxidative effects of homocysteine in vascular endothelial cells. Eur J Nutr 46, 286–292 (2007). https://doi.org/10.1007/s00394-007-0663-x

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  • DOI: https://doi.org/10.1007/s00394-007-0663-x

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