Hydroxytyrosol targets extracellular matrix remodeling by endothelial cells and inhibits both ex vivo and in vivo angiogenesis

Food Chem. 2017 Apr 15:221:1741-1746. doi: 10.1016/j.foodchem.2016.10.111. Epub 2016 Oct 24.


The health benefits of olive oil are attributed to their bioactive compounds, such as hydroxytyrosol. Previously, we demonstrated that hydroxytyrosol inhibits angiogenesis in vitro. The present study aimed to: i) get further insight into the effects of hydroxytyrosol on extracellular matrix remodeling; and ii) test whether hydroxytyrosol is able to inhibit angiogenesis ex vivo and in vivo. Hydroxytyrosol induced a shift toward inhibition of proteolysis in endothelial cells, with decreased expression of extracellular matrix remodeling-enzyme coding genes and increased levels of some of their inhibitors. Furthermore, this work demonstrated that hydroxytyrosol, at concentrations within the range of its content in virgin olive oil that can be absorbed from moderate and sustained virgin olive oil consumption, is a strong inhibitor of angiogenesis ex vivo and in vivo. These results suggest the need for translational studies to evaluate the potential use of hydroxytyrosol for angio-prevention and angiogenesis inhibition in clinical setting.

Keywords: Angiogenesis; Aortic ring assay; Bovine aorta endothelial cells (BAEC); Chorioallantoic membrane (CAM) assay; Hydroxytyrosol; Matrix metalloproteinase (MMP); Tissue inhibitor of metalloproteinase (TIMP); Urokinase-type plasminogen activator (uPA).

MeSH terms

  • Animals
  • Cattle
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / metabolism
  • Phenylethyl Alcohol / pharmacology
  • Proteolysis / drug effects


  • 3,4-dihydroxyphenylethanol
  • Phenylethyl Alcohol