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Title: Angiotensin converting enzyme inhibition reduces the expression of transforming growth factor-beta1 and type IV collagen in diabetic vasculopathy.
Austin Authors: Rumble, J R;Gilbert, Richard E;Cox, Allison J;Wu, L;Cooper, Mark E
Affiliation: Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Australia
Issue Date: 1-Nov-1998
Publication information: Journal of Hypertension; 16(11): 1603-9
Abstract: The purpose of this study was to assess the role of transforming growth factor (TGF)-beta1 in the development of diabetes-associated mesenteric vascular hypertrophy and in the antitrophic effect of angiotensin converting enzyme inhibitors.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-beta1 and alpha1 (type IV) collagen messenger (m)RNA levels were analysed by Northern analysis. Immunohistochemical analyses for TGF-beta1 and type IV collagen were also performed.The diabetic rats had increased mesenteric vessel weight at 3 weeks but not at 1 week and a concomitant rise in mesenteric TGF-beta1 and in alpha1 (type IV) collagen mRNA levels. Ramipril treatment attenuated mesenteric vessel hypertrophy and prevented the increase in TGF-beta1 and alpha1 (type IV) collagen mRNA levels after 3 weeks of diabetes. The immunohistochemical analysis revealed that diabetes was associated with increased TGF-beta1 and type IV collagen protein and extracellular matrix accumulation in mesenteric vessels, and this increase was reduced by ramipril treatment.These results support the concept that TGF-beta is involved in the changes associated with diabetic vascular disease, and suggest a mechanism by which angiotensin converting enzyme inhibitors exert their antitrophic effects.
Gov't Doc #: 9856360
Journal: Journal of Hypertension
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology
Blood Glucose.drug effects
Blood Pressure.drug effects
Blotting, Northern
Body Weight.drug effects
Diabetes Mellitus, Experimental.complications
Diabetic Angiopathies.complications.genetics.metabolism
Gene Expression.drug effects
RNA, Messenger.analysis.genetics
Rats, Sprague-Dawley
Transforming Growth Factor beta.genetics
Vascular Diseases.complications.genetics.metabolism
Appears in Collections:Journal articles

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