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

https://doi.org/10.1006/bbrc.2001.5232Get rights and content

Abstract

Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human coronary arteries, we determined if VEGF could stimulate VSMC migration and the intracellular signals involved. VEGF induced VSMC migration but had no significant activity on proliferation. VEGF increased intracellular reactive oxygen species (ROS), NF-κB activation and IL-6 expression. Blockade of the generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-κB activation, IL-6 expression, and cell migration indicating that generation of ROS was required for NF-κB activation and the chemotactic activity of VEGF. Expression of a mutated, nondegradable form of inhibitor of NF-κB (IκB-αM) suppressed VEGF-triggered activation of NF-κB and upregulation of IL-6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly attenuated the migration stimulated by VEGF. Collectively, our data provide the first evidence that intracellular ROS and NF-κB are required for VEGF-mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved in the ability of the growth factor to stimulate migration.

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    To whom correspondence should be addressed at Mercer University School of Medicine, 1550 College Street, Macon, GA 31207. Fax: 478-301-2913. E-mail: [email protected].

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