Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis

Filomena de Nigris, Sharon Williams-Ignarro, Vincenzo Sica, Lilach O Lerman, Francesco P. D'Armiento, Russell E. Byrns, Amelia Casamassimi, Daniela Carpentiero, Concetta Schiano, Daigo Sumi, Carmela Fiorito, Louis J. Ignarro, Claudio Napoli

Research output: Contribution to journalArticle

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Abstract

Background: 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-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of l-arginine to l-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC25 values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalCardiovascular Research
Volume73
Issue number2
DOIs
StatePublished - Jan 15 2007

Fingerprint

Punicaceae
Nitric Oxide Synthase Type III
Fruit
Atherosclerosis
Genes
Antioxidants
Isoprostanes
Citrulline
punicalagin
Cyclic GMP
Nitrates
Arginine
Oxidative Stress
Endothelial Cells

Keywords

  • Antioxidants
  • ELK-1
  • eNOS
  • Nitric oxide
  • p-CREB
  • Polyphenols
  • Pomegranate
  • Shear stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. / de Nigris, Filomena; Williams-Ignarro, Sharon; Sica, Vincenzo; Lerman, Lilach O; D'Armiento, Francesco P.; Byrns, Russell E.; Casamassimi, Amelia; Carpentiero, Daniela; Schiano, Concetta; Sumi, Daigo; Fiorito, Carmela; Ignarro, Louis J.; Napoli, Claudio.

In: Cardiovascular Research, Vol. 73, No. 2, 15.01.2007, p. 414-423.

Research output: Contribution to journalArticle

de Nigris, F, Williams-Ignarro, S, Sica, V, Lerman, LO, D'Armiento, FP, Byrns, RE, Casamassimi, A, Carpentiero, D, Schiano, C, Sumi, D, Fiorito, C, Ignarro, LJ & Napoli, C 2007, 'Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis', Cardiovascular Research, vol. 73, no. 2, pp. 414-423. https://doi.org/10.1016/j.cardiores.2006.08.021
de Nigris, Filomena ; Williams-Ignarro, Sharon ; Sica, Vincenzo ; Lerman, Lilach O ; D'Armiento, Francesco P. ; Byrns, Russell E. ; Casamassimi, Amelia ; Carpentiero, Daniela ; Schiano, Concetta ; Sumi, Daigo ; Fiorito, Carmela ; Ignarro, Louis J. ; Napoli, Claudio. / Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. In: Cardiovascular Research. 2007 ; Vol. 73, No. 2. pp. 414-423.
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abstract = "Background: 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-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of l-arginine to l-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC25 values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.",
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T1 - Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis

AU - de Nigris, Filomena

AU - Williams-Ignarro, Sharon

AU - Sica, Vincenzo

AU - Lerman, Lilach O

AU - D'Armiento, Francesco P.

AU - Byrns, Russell E.

AU - Casamassimi, Amelia

AU - Carpentiero, Daniela

AU - Schiano, Concetta

AU - Sumi, Daigo

AU - Fiorito, Carmela

AU - Ignarro, Louis J.

AU - Napoli, Claudio

PY - 2007/1/15

Y1 - 2007/1/15

N2 - Background: 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-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of l-arginine to l-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC25 values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.

AB - Background: 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-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of l-arginine to l-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC25 values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.

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KW - ELK-1

KW - eNOS

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