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.

[1]  D. Gaitini,et al.  Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. , 2004, Clinical nutrition.

[2]  C. Napoli,et al.  Oxidation-sensitive mechanisms, vascular apoptosis and atherosclerosis. , 2003, Trends in molecular medicine.

[3]  C. Watson,et al.  Mouse Macrophage Paraoxonase 2 Activity Is Increased Whereas Cellular Paraoxonase 3 Activity Is Decreased Under Oxidative Stress , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[4]  C. Napoli,et al.  Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Napoli,et al.  Beneficial effects of antioxidants and l-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[6]  E. Ackah,et al.  Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  G Mathé,et al.  Polyphenols: do they play a role in the prevention of human pathologies? , 2002, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[8]  C. Glass,et al.  Maternal Hypercholesterolemia During Pregnancy Promotes Early Atherogenesis in LDL Receptor-Deficient Mice and Alters Aortic Gene Expression Determined by Microarray , 2002, Circulation.

[9]  J. Folts.  Potential health benefits from the flavonoids in grape products on vascular disease. , 2002, Advances in experimental medicine and biology.

[10]  A. Hofman,et al.  Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. , 2002, Drugs under experimental and clinical research.

[11]  C. Napoli,et al.  Oxidation-sensitive transcription factors and molecular mechanisms in the arterial wall. , 2001, Antioxidants & redox signaling.

[12]  L. Mazzolai,et al.  Flow Pulsatility Is a Critical Determinant of Oxidative Stress in Endothelial Cells , 2001, Hypertension.

[13]  J. Stein,et al.  Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. , 2001, The American journal of cardiology.

[14]  M. Aviram,et al.  Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. , 2001, Atherosclerosis.

[15]  R. Coleman,et al.  Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. , 2001, The Journal of nutrition.

[16]  Larry V. McIntire,et al.  DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Keaney,et al.  Short- and Long-Term Black Tea Consumption Reverses Endothelial Dysfunction in Patients With Coronary Artery Disease , 2001, Circulation.

[18]  C. Napoli,et al.  Nitric oxide and atherosclerosis. , 2001, Nitric oxide : biology and chemistry.

[19]  G. Garcı́a-Cardeña,et al.  Biomechanical activation of vascular endothelium as a determinant of its functional phenotype , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Napoli,et al.  c-myc activation in early coronary lesions in experimental hypercholesterolemia. , 2001, Biochemical and biophysical research communications.

[21]  C. Napoli,et al.  Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Condorelli,et al.  Evidence for Oxidative Activation of c-Myc–Dependent Nuclear Signaling in Human Coronary Smooth Muscle Cells and in Early Lesions of Watanabe Heritable Hyperlipidemic Rabbits: Protective Effects of Vitamin E , 2000, Circulation.

[23]  C. Glass,et al.  Mildly Oxidized Low Density Lipoprotein Activates Multiple Apoptotic Signaling Pathways in Human Coronary Cells , 2022 .

[24]  F. Tomás-Barberán,et al.  Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. , 2000, Journal of agricultural and food chemistry.

[25]  M. Cybulsky,et al.  The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Coleman,et al.  Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. , 2000, The American journal of clinical nutrition.

[27]  C. Napoli,et al.  Nitric oxide as a signaling molecule in the vascular system: an overview. , 1999, Journal of cardiovascular pharmacology.

[28]  S Y Schubert,et al.  Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids. , 1999, Journal of ethnopharmacology.

[29]  M. Gimbrone.  Vascular Endothelium , Hemodynamic Forces , and Atherogenesis , 1999 .

[30]  H. Hsieh,et al.  Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear‐induced c‐fos expression , 1998, Journal of cellular physiology.

[31]  M. Aviram,et al.  Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis. , 1998, Atherosclerosis.

[32]  J. Shyy,et al.  Reactive oxygen species are involved in shear stress-induced intercellular adhesion molecule-1 expression in endothelial cells. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[33]  R. Coleman,et al.  Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[34]  M. Metche,et al.  Quantitative determination of the polyphenolic content of pomegranate peel , 1996, Zeitschrift fur Lebensmittel-Untersuchung und -Forschung.

[35]  Jon M. Fukuto,et al.  Shear Stress‐Induced Release of Nitric Oxide From Endothelial Cells Grown on Beads , 1991, Hypertension.

[36]  I. A. Ismail,et al.  Chemical composition of juice and seeds of pomegranate fruit , 1990 .

[37]  J. M. Liu,et al.  A study on tea-pigment in prevention of atherosclerosis. , 1989, Chinese medical journal.

[38]  D. Ku,et al.  Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. , 1988, Archives of pathology & laboratory medicine.

[39]  G. Hutchins,et al.  Correlation between intimal thickness and fluid shear in human arteries. , 1981, Atherosclerosis.