Tranilast attenuates vascular hypertrophy, matrix accumulation and growth factor overexpression in experimental diabetes

F. Bonnet, Z. Cao, M. E. Cooper, A. J. Cox, D. J. Kelly, R. E. Gilbert

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25 Citations (Scopus)

Abstract

Objectives: The growth factors transforming growth factor-β (TGF-β) and epidermal growth factor (EGF) have both been implicated in the hypertrophic structural changes in the vasculature that are characteristic features of both human and experimental diabetes. Recently, tranilast (N(3,4-dimethoxycinnamoyl)anthranilic acid), a drug used in the treatment of allergic and dermatological diseases, has also been reported to inhibit transforming growth factor-β (TGF-β)-mediated collagen formation. However, its effects on vascular hypertrophy in diabetes are unknown. The present study thus sought to determine the effects of tranilast on both TGF-β and EGF expression and mast cells in mediating the trophic vascular changes in experimental diabetes. Methods: Vessel morphology, growth factors and collagen gene expression and matrix deposition were examined in the mesenteric arteries of control rats treated with or without tranilast, and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without tranilast (200 mg/kg/day) during a 3-week period. Results: Compared with control animals, diabetic rats had significantly increased vessel weight, wall: lumen ratio, ECM accumulation, gene expression of TGF-β1, EGF, and both α1 (I) and α1 (IV) collagen. Tranilast treatment did not influence plasma glucose or systemic blood pressure. However, tranilast significantly reduced mesenteric weight, wall: lumen ratio and matrix deposition and also attenuated the overexpression of TGF-β1, EGF, and both α1 (I) and α1 (IV) collagen mRNA in diabetic rats. Conclusion: These findings indicate that tranilast ameliorates pathological vascular changes observed in experimental diabetes in association with reduced growth factor expression independent of blood glucose or systemic blood pressure.

Original languageEnglish
Pages (from-to)386-392
Number of pages7
JournalDiabetes & Metabolism
Volume29
Issue number4 I
DOIs
Publication statusPublished - Sept 2003
Externally publishedYes

Keywords

  • Diabetes
  • Growth Factor
  • TGF-β
  • Tranilast
  • Vasculature

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