Inhibition of Vascular Endothelial Growth Factor-Induced Angiogenesis by Resveratrol through Interruption of Src-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation

Lin∥, Ming–Tsan; Yen, Men‐Luh; Lin, Chia–Yi; Kuo, Min-Liang

doi:10.1124/mol.64.5.1029

Cited by 193 publications

(134 citation statements)

References 39 publications

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“…From the literature β-catenin is found to be a critical mediator during development and angiogenesis [24], which is phosphorylated in a cytosolic multiprotein complex containing adenomatous polyposis coli protein (APC), Axin and GSK-3β [24][25][26][27]. When phosphorylation of β-catenin is blocked, this allows β-catenin to accumulate and translocate into nucleus, where it forms a complex with T-cell transcription factors/lymphoid-enhancer binding factor (TCF/LEF) family of transcription factors and is able to activate or repress several important target genes, such as c-Myc, cyclin D1, fibronectin, VEGF, Bcl-2 and survivin [28][29][30][31]. VEGF expression was found to be increased in HC (1.15 fold), HCR (1.86 fold), HCS (1.3 fold), HCRS (1.5 fold) when compared to control group.…”

Section: Discussionmentioning

confidence: 99%

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

Penumathsa

Thirunavukkarasu

Koneru

et al. 2007

Journal of Molecular and Cellular Cardiology

152

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Hypercholesterolemia (HC) is a common health problem that significantly increases risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated cardioprotection through nitric oxide dependent mechanism. Therefore the present study was undertaken to determine whether combination therapy with statin and resveratrol are more cardioprotective than individual treatment groups in ischemic rat heart model. The rats were fed rats with 2% high cholesterol diet and after 8 weeks of high cholesterol diet the animals were treated with statin (1mg/kg bw/day) and resveratrol (20mg/kg bw/day) for 2 weeks. The rats were assigned to: 1) Control (C) 2) HC 3) HCR 4) HCS and 5) HCRS. The hearts, subjected to 30 min global ischemia followed by 120 min reperfusion were used as experimental model. The left ventricular functional recovery (+dp/dt) was found to be significantly better in the HCRS (1926±43), HCR (1556±65) and HCS (1635±40) compared to HC group (1127±16). The infarct size in the HCRS, HCS and HCR groups were 37±3.6, 43±3.3 and 44 ±4.2 respectively compared to 53±4.6 in HC. The lipid level was found to be decreased in all the treatment groups when compared to HC more significantly in HCS and HCRS groups when compared to HCR. Increased phosphorylation of Akt and eNOS was also observed in all the treatment groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of reduction in apoptosis was more significant in HCRS group compared to all other groups. In-vivo rat myocardial infarction (MI) model subjected to one week of permanent left descending coronary artery (LAD) occlusion documented increased capillary density in HCR and HCRS treated group when compared to HCS treatment group. We also documented increased β-catenin translocation and increased VEGF mRNA expression in all treatment groups. Thus, we conclude that the acute as well as chronic protection afforded by combination treatment with statin and resveratrol may be due to pro-angiogenic, antihyperlipidemic and anti-apoptotic effects and long term effects may be caused by increased neovascularization of the MI zone leading to less ventricular remodeling.

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Section: Discussionmentioning

confidence: 99%

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

Penumathsa

Thirunavukkarasu

Koneru

et al. 2007

Journal of Molecular and Cellular Cardiology

152

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“…70 Resveratrol, in turn, inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis by disrupting the activation of reactive oxygen species-dependent Src kinase. 71 Phenolic acids and their analogs (Table I) can also act through this chemopreventive mechanism.…”

Section: H Suppression Of Angiogenesismentioning

confidence: 99%

New insights on the anticancer properties of dietary polyphenols

et al. 2006

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Cancer, one of the major causes of death across the world, has shown to be a largely preventable disease, highly susceptible to modulation by dietary factors. Phenolic compounds, abundant in vegetables and fruits ubiquitous in diet, were described to play an important role as chemopreventive agents. Since conventional therapeutic and surgical approaches have not been able to control the incidence of most cancer types, the development of chemopreventive strategies is an urgent priority in public health. The current diet phenolic intake is often insufficient to protect from mutagens (either exogenous or endogenous), which leads to the need for dietary supplementation as an alternative approach. Research efforts are placing increasing emphasis on identifying the biological mechanisms and in particular the signal transduction pathways related to the chemopreventive activities of these compounds. These effects are believed to occur by the regulation of signaling pathways such as nuclear factor-kB (NF-kB), activator protein-1 (AP-1) or mitogen-activated protein kinases (MAPK). Dietary polyphenols can exert their effects on these pathways separately or sequentially and in addition the occurrence of crosstalk between these pathways cannot be overlooked. By modulating cell signaling pathways, polyphenols activate cell death signals and induce apoptosis in precancerous or malignant cells resulting in the inhibition of cancer development or progression. However, regulation of cell signaling pathways by dietary polyphenols can also lead to cell proliferation/survival or inflammatory responses due to increased expression of several genes. The present review summarizes the most recent advances providing new insights into the molecular mechanisms underlying the promising anticarcinogenic activity of dietary polyphenols. ß

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“…Because tyrosine phosphorylation of VE-cadherin is required for VEGF-induced dissociation of cell-cell contacts in ECs, 6,9,21 we examined whether IQGAP1 is involved in this response. As shown in Figure 4A, VEGF stimulation induced a significant increase in tyrosine phosphorylation of VEcadherin and IQGAP1 within 5 minutes.…”

Section: Iqgap1 Is Required For Ros-dependent Tyrosine Phosphorylatiomentioning

confidence: 99%

“…4 Tyrosine phosphorylation of the VE-cadherin complex is another mechanism that regulates the stability of cell-cell junctions, [5][6][7] which is in part mediated through reactive oxygen species (ROS). 8,9 We demonstrated that ROS derived from Rac1-dependent NAD(P)H oxidase play an important role in VEGF signaling and angiogenesis in ECs and in vivo. 10,11 Thus, the VE-cadherin-based endothelial adherens junction is a potential site for initial activation of VEGFR2-mediated, ROSdependent signaling linked to angiogenesis.…”

mentioning

confidence: 99%

IQGAP1 Mediates VE-Cadherin–Based Cell–Cell Contacts and VEGF Signaling at Adherence Junctions Linked to Angiogenesis

Yamaoka‐Tojo

Tojo

Kim

et al. 2006

ATVB

105

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Objective-Vascular endothelial growth factor (VEGF) induces angiogenesis by stimulating reactive oxygen species (ROS) production primarily through the VEGF receptor-2 (VEGFR2). One of the initial responses in established vessels to stimulate angiogenesis is loss of vascular endothelial (VE)-cadherin-based cell-cell adhesions; however, little is known about the underlying mechanisms. IQGAP1 is a novel VEGFR2 binding protein, and it interacts directly with actin, cadherin, and ␤-catenin, thereby regulating cell motility and morphogenesis. Methods and Results-Confocal microscopy analysis shows that IQGAP1 colocalizes with VE-cadherin at cell-cell contacts in unstimulated human endothelial cells (ECs). VEGF stimulation reduces staining of IQGAP1 and VE-cadherin at the adherens junction without affecting interaction of these proteins. Knockdown of IQGAP1 using siRNA inhibits localization of VE-cadherin at cell-cell contacts, VEGF-stimulated recruitment of VEGFR2 to the VE-cadherin/␤-catenin complex, ROS-dependent tyrosine phosphorylation of VE-cadherin, which is required for loss of cell-cell contacts and capillary tube formation. IQGAP1 expression is increased in a mouse hindlimb ischemia model of angiogenesis. Conclusions-IQGAP1 is required for establishment of cell-cell contacts in quiescent ECs. To induce angiogenesis, it may function to link VEGFR2 to the VE-cadherin containing adherens junctions, thereby promoting VEGF-stimulated, ROS-dependent tyrosine phosphorylation of VE-cadherin and loss of cell-cell contacts. (Arterioscler Thromb Vasc

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Inhibition of Vascular Endothelial Growth Factor-Induced Angiogenesis by Resveratrol through Interruption of Src-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation

Cited by 193 publications

References 39 publications

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

New insights on the anticancer properties of dietary polyphenols

IQGAP1 Mediates VE-Cadherin–Based Cell–Cell Contacts and VEGF Signaling at Adherence Junctions Linked to Angiogenesis

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