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

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.