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

被引:105
作者
de Nigris, F
Williams-Ignarro, S
Lerman, LO
Crimi, E
Botti, C
Mansueto, G
D'Armiento, FP
De Rosa, G
Sica, V
Ignarro, LJ [1 ]
Napoli, C
机构
[1] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[2] Univ Naples Federico II, Dept Gen Pathol, Sch Med, I-80131 Naples, Italy
[3] Univ Naples Federico II, Dept Med, Sch Med, I-80131 Naples, Italy
[4] Univ Naples Federico II, Dept Human Pathol, Sch Med, I-80131 Naples, Italy
[5] Univ Naples Federico II, Dept Clin Pathol, Sch Med, I-80131 Naples, Italy
[6] Univ Naples Federico II, Excellence Res Ctr Cardiovasc Dis 2, SUN, I-80138 Naples, Italy
[7] Univ Calif Los Angeles, Div Anesthesiol, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[9] Mayo Clin & Mayo Fdn, Div Hypertens, Rochester, MN 55905 USA
[10] Univ Novara, Dept Anesthesiol, I-28100 Novara, Italy
[11] Boston Univ, Evans Dept Med, Boston, MA 02118 USA
关键词
polyphenols; p-Jun; antioxidants;
D O I
10.1073/pnas.0500998102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4896 / 4901
页数:6
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