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Title: Attenuation of diabetes-associated mesenteric vascular hypertrophy with perindopril: morphological and molecular biological studies.
Austin Authors: Cooper, Mark E;Cao, Zemin;Rumble, J R;Jandeleit, K;Allen, Terri J;Gilbert, Richard E
Affiliation: Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia
Issue Date: 1-Dec-1998
Publication information: Metabolism: Clinical and Experimental; 47(12 Suppl 1): 24-7
Abstract: Vascular disease is now the major cause of morbidity and mortality in the diabetic population. Our group explored the vascular changes associated with experimental diabetes and examined whether these changes can be ameliorated by angiotensin-converting enzyme (ACE) inhibition. The ACE inhibitor perindopril (PE) was administered to streptozotocin-induced diabetic rats for 24 weeks. At death, mesenteric vessels were perfused in vivo followed by assessment of the vascular architecture by quantitative histomorphometry. In a subgroup of animals, RNA was extracted from the mesenteric vasculature for assessment of gene expression of the prosclerotic cytokine, transforming growth factor beta 1 (TGFbeta1), and the matrix protein, type IV collagen. Diabetes was associated with smooth muscle hypertrophy and extracellular matrix (ECM) accumulation. ECM accumulation, particularly collagen deposition, was observed in the medial and adventitial layers. ACE inhibition prevented mesenteric vascular hypertrophy after 24 weeks of diabetes. In addition, overexpression of TGFbeta1 in the vessels of diabetic animals was prevented by PE treatment. Similarly, type IV collagen mRNA levels were increased in diabetic vessels, and this overexpression was also prevented by PE therapy. In summary, ACE inhibition attenuates many of the vascular changes observed in experimental diabetes and may have important clinical implications as a vasoprotective agent in human diabetes.
Gov't Doc #: 9867067
Journal: Metabolism: clinical and experimental
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Blood Vessels.pathology
Diabetes Mellitus, Experimental.drug therapy.genetics.pathology
Diabetic Angiopathies.drug therapy.genetics.pathology
Indoles.therapeutic use
RNA, Messenger.metabolism
Rats, Sprague-Dawley
Splanchnic Circulation.drug effects
Transforming Growth Factor beta.genetics
Appears in Collections:Journal articles

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