Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects

doi:10.1016/S0008-6363(02)00699-5

Cardiovascular Research 2003 57(2):563-571; doi:10.1016/S0008-6363(02)00699-5
© 2003 by European Society of Cardiology

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Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects

Bastiaan van Dam^a^,d, Victor W.M van Hinsbergh^d^,e, Coen D.A Stehouwer^a^,d, Amanda Versteilen^b^,d, Henk Dekker^c, Rien Buytenhek^e, Hans M Princen^e and Casper G Schalkwijk^b^,d^,*

^aDepartment of Internal Medicine, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands
^bDepartment of Clinical Chemistry, Institute for Cardiovascular Research, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
^cDepartment of Oncology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands
^dInstitute for Cardiovascular Research, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands
^eGaubius Laboratory TNO-PG, Leiden, The Netherlands

c.schalkwijk{at}vumc.nl

^* Corresponding author. Tel.: +31-20-444-3680; fax: +31-20-444-3895.

Objective: In a combination of in vivo and in vitro studies,we investigated mechanisms via which ${alpha}$ -tocopherol, a lipid solubleform of vitamin E, can directly affect endothelial activationas induced by H₂O₂ and TNF ${alpha}$ . Methods: We measured effects of ${alpha}$ -tocopherol on H₂O₂-induced lipid peroxidation as determinedwith a fluorescent C-11 BODIPY^581/591 probe and on adhesionmolecule expression in cultured endothelial cells. In 20 healthyvolunteers treated with increasing doses of ${alpha}$ -tocopherol up to800 IU/ml for 12 weeks, plasma levels of soluble cell adhesionmolecules (sCAMs) and C-reactive protein were measured. Results:We showed that ${alpha}$ -tocopherol protects cultured endothelial cellsagainst H₂O₂-induced lipid peroxidation, while TNF ${alpha}$ did not inducelipid peroxidation. Moreover, ${alpha}$ -tocopherol attenuated H₂O₂-,but not TNF ${alpha}$ -induced increases in adhesion molecule expression.In healthy persons, ${alpha}$ -tocopherol decreased plasma levels of sE-selectinfrom 65±6 to 60±6 ng/ml (P=0.002), sVCAM from893±31 to 853±23 ng/ml (P=0.022), and sICAM from483±21 to 463±16 ng/ml (P=0.048). C-Reactive protein,as a sensitive marker of low grade inflammation, was not significantlyaffected. Conclusion: ${alpha}$ -Tocopherol specifically inhibits lipidperoxidation-induced endothelial activation in vitro. The observedvitamin E-induced decrease in sCAMs in control subjects suggeststhat lipid peroxidation can take place in healthy individuals.Although vitamin E supplementation may be especially effectivein specific groups of patients exposed to increased oxidativestress, our study suggests that vitamin E supplementation canbe of benefit in healthy individuals as well.

KEYWORDS Endothelial function; Free radicals; Lipid metabolism

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