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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 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/13636 | Journal: | Metabolism: clinical and experimental | URL: | https://pubmed.ncbi.nlm.nih.gov/9867067 | Type: | Journal Article | Subjects: | Angiotensin-Converting Enzyme Inhibitors.therapeutic use Animals Blood Vessels.pathology Diabetes Mellitus, Experimental.drug therapy.genetics.pathology Diabetic Angiopathies.drug therapy.genetics.pathology Hypertrophy Indoles.therapeutic use Male Perindopril RNA, Messenger.metabolism Rats Rats, Sprague-Dawley Splanchnic Circulation.drug effects Transforming Growth Factor beta.genetics |
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