Red Wine Polyphenols Inhibit Proliferation of Vascular Smooth Muscle Cells and Downregulate Expression of Cyclin A Gene

Iijima, Katsuya; Yoshizumi, Masao; Hashimoto, Masayoshi; Kim, Seungbum; Eto, Masato; Ako, Junya; Liang, Yi-Qiang; Sudoh, Noriko; Hosoda, Kazuaki; Nakahara, Kiyoshi; Toba, Kenji; Ouchi, Yasuyoshi

doi:10.1161/01.cir.101.7.805

Cited by 104 publications

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“…12 In the present study, RWPs strongly inhibited the proliferation and DNA synthesis of PDGF-BB-stimulated SMCs; however, the ERK1/2 phosphorylation, which is known to relate to cell growth, 17 was not inhibited by RWPs (up to 30 g/mL). These results suggest that the inhibitory effects of RWPs on cell-cycle progression in SMCs do not depend on the ERK1/2 pathway.…”

Section: Discussioncontrasting

confidence: 60%

“…12 It is well known that the ERK1/2 pathway is important in growth factor-induced proliferation. 17 However, PDGF-BB-induced activation of ERK1/2 in SMCs was not significantly inhibited by RWPs, as shown in Figure 4B.…”

Section: Resultsmentioning

confidence: 99%

“…12 The total RWP fraction (24 g total) was obtained by eluting the column with 100% ethanol. This compound was dissolved in 50% ethanol using ultrasonication.…”

Section: Preparation Of Red Wine Polyphenolic Compoundmentioning

confidence: 99%

“…11 We have recently shown that RWPs inhibit SMC proliferation and that the downregulation of a cell-cycle regulator, cyclin A, is at least in part responsible for this growth inhibition. 12 However, the effect of RWPs on SMC migration is not known. Thus, in the present study, we investigated whether RWPs could affect PDGF-BB-induced SMC migration and activation of intracellular signaling pathways that are known to mediate cell migration.…”

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confidence: 99%

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Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways

et al. 2002

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Background-Red wine polyphenols (RWPs) have been shown to have an antiatherogenic activity mainly through antioxidative effects on LDL oxidation. Although vascular smooth muscle cell (SMC) migration is critical to atherosclerosis formation, the effect of RWPs on SMC migration has not been elucidated. In this study, we investigated whether RWPs could affect the migration of cultured SMCs stimulated by growth factors. Methods and Results-RWP concentration dependently inhibited platelet-derived growth factor (PDGF)-BB-induced and serum-induced SMC migration in wounding assay and Boyden chamber assay. However, these inhibitory effects of RWPs were not seen in serum-stimulated vascular endothelial cell migration in either assay. Moreover, specific inhibitors of phosphatidylinositol-3Ј kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK ), but not of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), reduced PDGF-BB-induced SMC migration. To elucidate the signaling mechanism underlying the RWP effects, we investigated the effects of RWPs on the activity of PI3K and the phosphorylation of MAPK pathways in PDGF-BB-stimulated SMCs. RWPs inhibited the PI3K activity and p38MAPK phosphorylation, but not ERK1/2 phosphorylation, in a concentration-dependent manner. Moreover, the phosphorylation of MKK3/6, an upstream kinase of p38 MAPK , was also inhibited by RWP treatment in a concentrationdependent manner, suggesting that the inhibitory effect of RWPs on the p38 MAPK pathway works upstream of MKK3/6. The concentration-effect relationship of RWPs necessary for the inhibition of PI3K and p38MAPK pathways was similar to that of cell migration assays. Conclusions-RWPs inhibit the SMC migration through the inhibition of 2 distinct signaling pathways and thus exert antiatherogenic actions.

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Section: Discussioncontrasting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

“…12 The total RWP fraction (24 g total) was obtained by eluting the column with 100% ethanol. This compound was dissolved in 50% ethanol using ultrasonication.…”

Section: Preparation Of Red Wine Polyphenolic Compoundmentioning

confidence: 99%

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Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways

et al. 2002

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“…Apoprotein E (Apo E)-deficient mice also showed reduced atherosclerosis progression when fed RW (14). RW also causes monocyte chemotactic protein-1 expression blockade and reduced neointimal hyperplasia after balloon injury in rabbits (15), inhibition of smooth muscle cell proliferation and of cyclin A expression (16), as well as inhibition of the plateletderived growth factor receptor by RW flavonoids in cultured smooth muscle cells (17) -all of them factors contributing to atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients

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Brandizzi

et al. 2005

Braz J Med Biol Res

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Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6 ± 8.1 years) without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice (GJ), 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0 ± 28.7 mg/dl) but HDL, triglycerides, glucose, adhesion molecules, and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0 ± 7.1 vs 12.1 ± 4.5%; P < 0.05) and increased with both GJ (10.1 ± 7.1 before vs 16.9 ± 6.7% after: P < 0.05) and RW (10.1 ± 6.4 before vs 15.6 ± 4.6% after; P < 0.05). RW, but not GJ, also significantly increased endothelium-independent vasodilation (17.0 ± 8.6 before vs 23.0 ± 12.0% after; P < 0.01). GJ reduced ICAM-1 but not VCAM and RW had no effect on either molecule. No significant alterations were observed in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the additional negative effects of alcohol despite the gender.

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Integrierte Hybridsysteme aus Nanopartikeln und Biomolekülen: Synthese, Eigenschaften und Anwendungen

2004

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Metall‐ oder Halbleiter‐Nanopartikel und Nanostäbchen haben ähnliche Dimensionen wie Proteine (Enzyme, Antigene, Antikörper) oder DNA. Die Integration von Nanopartikeln (mit ihren besonderen elektronischen, photonischen und katalytischen Eigenschaften) mit Biomaterialien (mit ihren einzigartigen Erkennungsmechanismen sowie katalytischen und inhibierenden Fähigkeiten) ergibt hybride Nanobiomaterialien mit synergistischen Eigenschaften und Funktionen. Dieser Aufsatz beschreibt die aktuellsten Entwicklungen bei der Synthese von Hybridsystemen aus Biomolekülen und Nanopartikeln oder Nanostäbchen und deren Anwendung zum Aufbau von geordneten 2D‐ und 3D‐Strukturen in Lösung und auf Oberflächen. Schwerpunkte sind der Einsatz von Biomolekül‐Nanopartikel‐Konjugaten für die Bioanalytik sowie zur Herstellung bioelektronischer Funktionseinheiten und Nanoleiterbahnen aus Metall, Halbleitern oder magnetischen Materialien.

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Red Wine Polyphenols Inhibit Proliferation of Vascular Smooth Muscle Cells and Downregulate Expression of Cyclin A Gene

Cited by 104 publications

References 32 publications

Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways

Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways

The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients

Integrierte Hybridsysteme aus Nanopartikeln und Biomolekülen: Synthese, Eigenschaften und Anwendungen

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