Planta Med 2007; 73 - P_557
DOI: 10.1055/s-2007-987337

No evidence for modulation of endothelial nitric oxide synthase by the olive oil polyphenol hydroxytyrosol in human endothelial cells

CA Schmitt 1, N Handler 2, EH Heiss 1, T Erker 2, VM Dirsch 1
  • 1University of Vienna, Department of Pharmacognosy, Althanstraße 14, 1090 Vienna, Austria
  • 2University of Vienna, Department of Medicinal Chemistry, Althanstraße 14, 1090 Vienna, Austria

Decreased nitric oxide (NO) availability in the vascular system is associated with atherosclerosis [1]. Upregulation of endothelial nitric oxide synthase (eNOS) expression and activity is considered as a strategy for the prevention of cardiovascular diseases.

Olive oil is a cornerstone of the Mediterranean diet. Besides fat, it contains several phenolic compounds which are found especially in extra virgin olive oil. The polyphenolic fraction seems to contribute considerably to the beneficial effects associated with olive oil consumption. The polyphenol hydroxytyrosol (HT), which is present in olive oil and red wine, has shown antiatherogenic activity in vitro and in vivo [2],[3].

To elucidate underlying molecular mechanisms, we investigated possible effects of HT on eNOS using human endothelial cells (EA.hy926) [4]. Specifically, we addressed putative effects on eNOS promoter transactivation, eNOS enzyme activity and NO availability. Cells were treated with a broad range of HT concentrations (from 10 nM to 100µM) and for different incubation times (15min to 24h). HT did not exert significant positive effects on eNOS in any of our assay systems. Neither did we find evidence for a possible synergism between the red wine polyphenol resveratrol and HT. We conclude that a direct modulation of eNOS is unlikely to account for the antiatherogenic properties of HT under non-inflammatory conditions of the endothelium.

Acknowledgements: The authors would like to thank Dr. C.-J.S. Edgell (University of North Carolina) for EA.hy926 cells, Dr. P. Wohlfahrt (sanofi-aventis, Germany) for EA.hy926-heNOS-Luc-cells and Drs Steffen Hering and Oskar Hoffmann for lab space to perform experiments with radioactive isotopes.

References: [1] Förstermann U (2006) Biol Chem 387: 1521–33. [2] Carluccio MA et al. (2003) Arterioscler Thromb Vasc Biol 23: 622–9. [3] Gonzalez-Santiago et al. (2006) Atherosclerosis 188: 35–42. [4] Edgell C-JS, et al. (1983) Proc Natl Acad Sci USA 80: 3734–3737.