Reactive Oxygen and NF-κB in VEGF-Induced Migration of Human Vascular Smooth Muscle Cells

Wang, Zhongbiao; Castresana, Manuel R.; Newman, Walter H.

doi:10.1006/bbrc.2001.5232

Cited by 99 publications

(70 citation statements)

References 31 publications

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“…1B). This is consistent with reports showing that VEGF induced activation of NF-B in bovine retinal microvascular ECs, human umbilical vein ECs, and human vascular smooth muscle cells (24,34,34,51). VEGF has also been shown to cause the phosphorylation of IB-␣, a signaling event downstream of the activation of IKK, in HN33 cell lines (20).…”

Section: Discussionsupporting

confidence: 91%

Shear stress and VEGF activate IKK via the Flk-1/Cbl/Akt signaling pathway

Wang

Chang

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Vascular endothelial cells are continuously exposed to mechanical (e.g., shear stress) and chemical (e.g., growth factors) stimuli. It is important to elucidate the mechanisms by which cells perceive and integrate these different stimuli to regulate the downstream signaling pathways. We (50) have previously reported the shear-induced interplay between two membrane receptors, integrins and Flk-1. In the present study, we investigated the molecular mechanisms regulating the downstream IB kinase (IKK) pathway in response to shear stress and VEGF. Both shear stress and VEGF induced a transient increase of IKK activity. These effects were inhibited by SU-1498, a specific Flk-1 inhibitor, and by a negative mutant of Casitas B-lineage lymphoma (Cbl) with tyrosine-to-phenylalanine mutations at sites 700, 731, and 774 (Cbl nm). Because Flk-1 and Cbl form a complex upon shearing or VEGF applications (50), these results suggest that shear stress and VEGF activate IKK via the receptor Flk-1 and its recruitment of the adapter protein Cbl. The inhibition of the shear-and VEGF-induced IKK activities by a negative mutant of Akt indicates that Akt acts upstream to IKK in response to shear stress and VEGF. Furthermore, SU-1498 and Cbl-nm abolished the shear-and VEGF-induced Akt activity, indicating that Akt acts at a level downstream to Flk-1 and Cbl. Therefore, our results indicate that the signaling events induced by shear stress and VEGF converge at the membrane receptor Flk-1 and that these stimuli share the Flk-1/Cbl/Akt pathway in activating IKK activation.

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Section: Discussionsupporting

confidence: 91%

Shear stress and VEGF activate IKK via the Flk-1/Cbl/Akt signaling pathway

Wang

Chang

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Basal levels of VSMC migration were different between the 2 strains (data not shown), in accordance with previous reports. 39 Previous studies have associated increased ROS levels 40,41 and activation of c-Src 42 with VSMC migration. However, there are no data showing that testosterone induces VSMC migration.…”

Section: Discussionmentioning

confidence: 99%

Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src–Dependent Pathways

et al. 2012

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Abstract-Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). The mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10 Ϫ7 mol/L, 0 -120 minutes).

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“…In arterial segments, smooth muscle cells generate VEGF in response to hypoxia, mechanical forces, and growth factors (e.g., basic FGF) (Brogi et al, 1994;Stavri et al, 1995;Couffinhal et al, 1997;Bausero et al, 2000;Quinn et al, 2002). Endothelial cell migration and proliferation are stimulated by VEGF via the receptor flk-1 (Nicosia et al, 1997), but only smooth muscle cell migration responds to VEGF (Grosskreutz et al, 1999;Wang Z et al, 2001). Following MCA:O, all of these elements are set in motion.…”

Section: Angiogenesismentioning

confidence: 99%

Cerebral Microvessel Responses to Focal Ischemia

Zoppo

Mabuchi

2003

J Cereb Blood Flow Metab

539

449

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Summary:Cerebral microvessels have a unique ultrastructure form, which allows for the close relationship of the endothelium and blood elements to the neurons they serve, via intervening astrocytes. To focal ischemia, the cerebral microvasculature rapidly displays multiple dynamic responses. Immediate events include breakdown of the primary endothelial cell permeability barrier, with transudation of plasma, expression of endothelial cell-leukocyte adhesion receptors, loss of endothelial cell and astrocyte integrin receptors, loss of their matrix ligands, expression of members of several matrix-degrading protease families, and the appearance of receptors associated with angiogenesis and neovascularization. These events occur pari passu with neuron injury. Alterations in the microvessel matrix after the onset of ischemia also suggest links to changes in nonvascular cell viability. Microvascular obstruction within the ischemic territory occurs after occlusion and reperfusion of the feeding arteries ("focal no-reflow" phenomenon). This can result from extrinsic compression and intravascular events, including leukocyte(-platelet) adhesion, platelet-fibrin interactions, and activation of coagulation. All of these events occur in microvessels heterogeneously distributed within the ischemic core. The panorama of acute microvessel responses to focal cerebral ischemia provide opportunities to understand interrelationships between neurons and their microvascular supply and changes that underlie a number of central nervous system neurodegenerative disorders.

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Reactive Oxygen and NF-κB in VEGF-Induced Migration of Human Vascular Smooth Muscle Cells

Cited by 99 publications

References 31 publications

Shear stress and VEGF activate IKK via the Flk-1/Cbl/Akt signaling pathway

Shear stress and VEGF activate IKK via the Flk-1/Cbl/Akt signaling pathway

Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src–Dependent Pathways

Cerebral Microvessel Responses to Focal Ischemia

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