Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress

Filomena De Nigris, Sharon Williams-Ignarro, Lilach O. Lerman, Ettore Crimi, Chiara Botti, Gelsomina Mansueto, Francesco P. D'Armiento, Gaetano De Rosa, Vincenzo Sica, Louis J. Ignarro, Claudio Napoli

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN) in the endothelium. Evidence suggests that polyphenolic antioxidants contained in the juice derived from the pomegranate can contribute to the reduction of oxidative stress and atherogenesis. The aim of the present study was to evaluate the effects of intervention with pomegranate juice (PJ) on oxidation-sensitive genes and endothelial NO synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Cultured human coronary artery endothelial cells (EC) exposed to high shear stress in vitro and hypercholesterolemic mice were used in this study. PJ concentrate reduced the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased eNOS expression (which was decreased by perturbed shear stress) in cultured EC and in atherosclerosis-prone areas of hypercholesterolemic mice. Moreover, oral administration of PJ to hypercholesterolemic mice at various stages of disease reduced significantly the progression of atherosclerosis. This experimental study indicates that the proatherogenic effects induced by perturbed shear stress can be reversed by chronic administration of PJ. This approach may have implications for the prevention or treatment of atherosclerosis and its clinical manifestations.

Original languageEnglish (US)
Pages (from-to)4896-4901
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number13
DOIs
StatePublished - Mar 29 2005

Keywords

  • Antioxidants
  • Polyphenols
  • p-Jun

ASJC Scopus subject areas

  • General

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