Olive Oil Polyphenol Oleuropein Inhibits Smooth Muscle Cell Proliferation

Objectives: The Mediterranean diet, with a high content of olive oil, is associated with a reduced risk of coronary artery disease. The aim of this study was to determine the effect of oleuropein, one of the polyphenols in olive oil, on vascular smooth muscle cell (SMC) proliferation in vitro. Design: This was an experimental study. Materials and methods: Bovine vascular SMCs were cultured in the presence of 100 mu M of oleuropein. On days 1, 3 and 5, cell number was counted. Cell cycle analysis was performed by flow cytometry. Cell cycle regulators were assessed by immunoblotting. Results: Cell proliferation in the presence of oleuropein was significantly inhibited by 92%. Cell cycle analysis revealed that oleuropein treatment blocked cells in the G1-S phase compared with the non-treated group. Among G1 phase regulators, retinoblastoma protein, cyclinD, p21 and p27 were not affected by oleuropein, but extracellular signal-regulated kinase 1/2 (ERK1/2) activation was inhibited. Growth of SMC treated with 100 mu of the mitogen-activated protein (MAP) kinase/ERK kinase 1 (MEK1) inhibitor P098059 was also significantly inhibited by 70%. Conclusions: Oleuropein inhibited SMC proliferation through a cell cycle block between the G1 and the S phases, which may be regulated by ERK1/2. These results suggest a mechanism by which olive oil consumption may have beneficial effects on cardiovascular mortality by inhibiting SMC proliferation. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.