Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2005 Mar 29;102(13):4896-901.
doi: 10.1073/pnas.0500998102. Epub 2005 Mar 21.

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

Filomena de Nigris  1 , 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
Affiliations
Comparative Study

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

Filomena de Nigris et al. Proc Natl Acad Sci U S A. .

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.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Effect of shear stress (0, 1, or 15 dynes per cm2) on eNOS, ELK-1, and p-Jun protein levels measured by Western blot in cultured human coronary artery EC. Control EC (0) or EC treated with 7 or 14 μl of PJ were exposed to laminar shear stress for 24 h.
Fig. 2.
Fig. 2.
Effects of PJ on high-prone (HP) aortic atherosclerotic lesion areas in hypercholesterolemic mice. (A and B) Comparison of the extent of lipid staining by oil red O in representative sections of the aorta of a placebo treated-control mouse (A) and in a PJ-treated mouse (B) from experimental protocol 1. Cryosections 10-μm-thick were stained with oil red O and counterstained with hematoxylin. (C and D) Comparisons of representative sections of the aortic complex lesions of a placebo-treated control mouse (C) and in a PJ-treated mouse (D) from experimental protocol 2. (E and F) Immunohistochemical staining of aortic sections for macrophages of a placebo-treated control mouse (E) and in a PJ-treated mouse (F) from experimental protocol 1. (G and H) The same immunostaining in a control mouse (G) and in a PJ-treated mouse (H) from the experimental protocol 2. (I-L) Immunohistochemical staining of aortic sections for oxidation-specific epitopes (MDA-2 monoclonal antibody). Placebo-treated control mouse (I) and PJ-treated mouse (J) from experimental protocol 1. The same immunostaining in a control mouse (K) and in a PJ-treated mouse (L) from experimental protocol 2. See Materials and Methods for more technical details. (Magnification: A-H, ×63; I-L, ×125.)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Buga, G. M., Gold, M. E. & Ignarro, L. J. (1991) Hypertension 17, 187-193. - PubMed
    1. Gimbrone, M. A., Jr. (1999) Am. J. Pathol. 155, 1-5. - PMC - PubMed
    1. Friedman, M. H., Hutchins, G. M., Bergerson, C. B., Deters, O. J. & Mark, F. F. (1981) Atherosclerosis 39, 425-436. - PubMed
    1. Glagov, S., Zarins, C., Giddens, D. P. G. & Ku, D. N. (1988) Arch. Pathol. Lab. Med. 112, 1018-1031. - PubMed
    1. de Nigris, F., Lerman, L. O., Condorelli, M., Lerman, A. & Napoli, C. (2001) Antioxid. Redox Signal. 3, 1119-1130. - PubMed

Publication types

MeSH terms

  NODES
admin 2
twitter 2