Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2/heme oxygenase-1 pathway

Phytomedicine. 2013 Sep 15;20(12):1088-94. doi: 10.1016/j.phymed.2013.05.002. Epub 2013 Jun 25.

Abstract

Endothelial progenitor cells (EPCs) are responsible for neovascularization of ischaemic tissue and may participate in re-endothelization of an injured arterial wall. There is evidence that angiotensin II, by an increase of gp91phox expression and induction of ROS generation, accelerates cell senescence and impairs functions of EPCs. Oleacein is a main phenolic compound from olive oil, whereas oleuropein is present in olive leaves. Both compounds possess antioxidative, hypotensive and anti-inflammatory properties and show beneficial activity on the cardiovascular system. In this study, we examined whether oleoeuropein and oleacein could protect EPCs against impairment of their functions due to angiotensin-induced cell senescence. CD31(+)/VEGFR-2(+) cells were isolated from young healthy volunteers blood samples and cultured on fibronectin-coated plates with angiotensin (1.0μM) in presence or absence of increasing concentrations (from 1.0 to 10.0 μM) of oleoeuropein or oleacein. As compared to angiotensin II-treated cells, EPCs exposed to oleacein or oleuropein prior to angiotensin II showed a significant increase of proliferation and telomerase activity, and a decrease in the percentage of senescent cells and intracellular ROS formation. Oleacein and oleuropein restored migration, adhesion and tube formation of EPCs diminished by angiotensin II in a concentration-dependent manner. This effect was related to NF-E2-related factor 2 (Nrf2) transcription factor activation and the increase of heme oxygenase-1 (HO-1) expression.

Keywords: Angiotensin II; Endothelial progenitor cells; Heme oxygenase-1; Nrf2; Olea europaea; Oleacein; Oleuropein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldehydes / chemistry
  • Aldehydes / pharmacology*
  • Angiotensin II / pharmacology*
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence / drug effects
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Healthy Volunteers
  • Heme Oxygenase-1 / drug effects*
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Iridoid Glucosides
  • Iridoids
  • NF-E2-Related Factor 2 / drug effects*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Pyrans / chemistry
  • Pyrans / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Stem Cells / drug effects*
  • Stem Cells / metabolism

Substances

  • Aldehydes
  • Iridoid Glucosides
  • Iridoids
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Phenols
  • Pyrans
  • Reactive Oxygen Species
  • oleacein
  • Angiotensin II
  • oleuropein
  • Heme Oxygenase-1