Role for heparin-binding growth factors in glucose-induced vascular dysfunction

Clifford C. Stephan, Katherine C. Chang, Wanda Lejeune, David Erichsen, Robert J. Bjercke, Ajay Rege, Ronald J. Biediger, Timothy P. Kogant, Tommy A. Brock, Joseph R. Williamson, Ronald G. Tilton

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Vascular hyperpermeability and excessive neovascularization are hallmarks of early and late vascular endothelial cell dysfunction induced by diabetes. Vascular endothelial growth factor (VEGF) appears to be an important mediator for these early and late vascular changes. We reported previously, using skin chambers mounted on backs of SD rats, that neutralizing antibodies directed against VEGF blocked vascular permeability and blood flow changes induced by elevated tissue glucose and sorbitol levels in a dosage-dependent manner. We report in this study, using the same skin chamber model and neutralizing antibodies directed against basic fibroblast growth factor (FGF-2), that another member of the heparin-binding growth factor family also mediates glucose- and sorbitol-induced vascular permeability and blood flow increases. In addition, we show that 1) TBC1635, a novel heparin-binding growth factor antagonist, blocks the vascular hyperpermeability and blood flow increases induced by elevated tissue levels of glucose and sorbitol and by topical application of VEGF and FGF-2 to granulation tissue in skin chambers, and 2) suramin, a commercially available growth factor antagonist, blocks glucose-induced vascular dysfunction. These results suggest an early role for heparin-binding growth factors in the vascular dysfunction caused by excessive glucose metabolism, possibly via the sorbitol pathway.

Original languageEnglish (US)
Pages (from-to)1771-1778
Number of pages8
JournalDiabetes
Volume47
Issue number11
DOIs
StatePublished - Oct 28 1998

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Stephan, C. C., Chang, K. C., Lejeune, W., Erichsen, D., Bjercke, R. J., Rege, A., Biediger, R. J., Kogant, T. P., Brock, T. A., Williamson, J. R., & Tilton, R. G. (1998). Role for heparin-binding growth factors in glucose-induced vascular dysfunction. Diabetes, 47(11), 1771-1778. https://doi.org/10.2337/diabetes.47.11.1771