Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress.
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.
de Nigris
Filomena
F
Department of General Pathology, School of Medicine, University of Naples, 80131 Naples, Italy.
Williams-Ignarro
Sharon
S
Lerman
Lilach O
LO
Crimi
Ettore
E
Botti
Chiara
C
Mansueto
Gelsomina
G
D'Armiento
Francesco P
FP
De Rosa
Gaetano
G
Sica
Vincenzo
V
Ignarro
Louis J
LJ
Napoli
Claudio
C
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D003326:Coronary Circulation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005638:Fruit / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D028421:Isoprostanes / Q000097:blood; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D028321:Plant Preparations / Q000494:pharmacology* / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency; D014157:Transcription Factors / Q000378:metabolism; D050807:ets-Domain Protein Elk-1
D000975:Antioxidants; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494113:Elk1 protein, mouse; D028421:Isoprostanes; D028321:Plant Preparations; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D002784:Cholesterol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse