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Reciprocal relation between VEGF and NO in the regulation of endothelial integrity

Nature Medicine volume 3, pages 879–886 (1997)Cite this article

Abstract

Balloon angioplasty disrupts the protective endothelial lining of the arterial wall, rendering arteries susceptible to thrombosis and intimal thickening. We show here that vascular endothelial growth factor (VEGF), an endothelial cell mitogen, is upregulated in medial smooth muscle cells of the arterial wall in response to balloon injury. Both protein kinase C (PKC) and tyrosine kinase pp60src mediate augmented VEGF expression. In contrast, nitric oxide (NO) donors inhibit PKC-induced VEGF upregulation by interfering with binding of the transcription factor activator protein-1 (AP-1) to the VEGF promoter. Inhibition of VEGF promoter activation suggests that NO secreted by a restored endothelium functions as the negative feedback mechanism that downregulates VEGF expression to basal levels. Administration of a neutralizing VEGF antibody impaired reendothelialization following balloon injury performed in vivo. These findings establish a reciprocal relation between VEGF and NO in the endogenous regulation of endothelial integrity following arterial injury.

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Author notes

  1. Jeffrey M. Isner: Correspondence should be addressed to J.M.I.

  2. Yukio Tsurumi and Toyoaki Murohara: Y.T. and T.M. contributed equally to this work.

Authors and Affiliations

  1. Departments of Medicine (Cardiology), Biomedical Research, St. Elizabeth's Medical Center of Boston, Tufts University School of Medicine, 736 Cambridge Street, Boston, Massachusetts, 02135, USA

    Yukio Tsurumi, Toyoaki Murohara, Kevin Krasinski, Dongfen Chen, Bernhard Witzenbichler, Marianne Kearney, Thierry Couffinhal & Jeffrey M. Isner

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Tsurumi, Y., Murohara, T., Krasinski, K. et al. Reciprocal relation between VEGF and NO in the regulation of endothelial integrity. Nat Med 3, 879–886 (1997). https://doi.org/10.1038/nm0897-879

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