Angiotensin converting enzyme inhibition reduces the expression of transforming growth factor-β1 and type IV collagen in diabetic vasculopathy

Jonathan R. Rumble, Richard E. Gilbert, Alison Cox, Leonard Wu, Mark E. Cooper

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Abstract

Objective. The purpose of this study was to assess the role of transforming growth factor (TGF)-β1 in the development of diabetes-associated mesenteric vascular hypertrophy and in the antitrophic effect of angiotensin converting enzyme inhibitors. Design and methods. Streptozotocin-induced diabetic and control Sprague-Dawley rats were randomly allocated to treatment with the angiotensin converting enzyme inhibitor ramipril or to no treatment and were killed 1 or 3 weeks after the streptozotocin injection. Blood was collected and mesenteric vessels removed. Mesenteric vascular weight was measured and TGF-β1 and α1 (type IV) collagen messenger (m)RNA levels were analysed by Northern analysis. Immunohistochemical analyses for TGF-β1 and type IV collagen were also performed. Results. The diabetic rats had increased mesenteric vessel weight at 3 weeks but not at 1 week and a concomitant rise in mesenteric TGF-β1 and in α1 (type IV) collagen mRNA levels. Ramipril treatment attenuated mesenteric vessel hypertrophy and prevented the increase in TGF-β1 and α1 (type IV) collagen mRNA levels after 3 weeks of diabetes. The immunohistochemical analysis revealed that diabetes was associated with increased TGF-β1 and type IV collagen protein and extracellular matrix accumulation in mesenteric vessels, and this increase was reduced by ramipril treatment. Conclusions. These results support the concept that TGF-β1 is involved in the changes associated with diabetic vascular disease, and suggest a mechanism by which angiotensin converting enzyme inhibitors exert their antitrophic effects.

Original languageEnglish
Pages (from-to)1603-1609
Number of pages7
JournalJournal of Hypertension
Volume16
Issue number11
DOIs
Publication statusPublished - 1 Jan 1998
Externally publishedYes

Keywords

  • Angiotensin converting enzyme inhibition
  • Angiotensin II
  • Diabetes mellitus
  • Mesenteric arteries
  • Transforming growth factor-β

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