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Title: | Prevention of accelerated atherosclerosis by angiotensin-converting enzyme inhibition in diabetic apolipoprotein E-deficient mice. | Austin Authors: | Candido, Riccardo;Jandeleit-Dahm, Karin A;Cao, Zemin;Nesteroff, Stefan P;Burns, Wendy C;Twigg, Stephen M;Dilley, Rodney J;Cooper, Mark E;Allen, Terri J | Affiliation: | Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg West, Australia | Issue Date: | 9-Jul-2002 | Publication information: | Circulation; 106(2): 246-53 | Abstract: | Atherosclerosis is a major complication of diabetes, but the mechanisms by which diabetes promotes macrovascular disease have not been fully delineated. Although several animal studies have demonstrated that inhibition of ACE results in a decrease in the development of atherosclerotic lesions, information about the potential benefits of these agents on complex and advanced atherosclerotic lesions as observed in long-term diabetes is lacking. The aim of this study was to evaluate whether treatment with the ACE inhibitor perindopril affects diabetes-induced plaque formation in the apolipoprotein E (apoE)-deficient mouse.Diabetes was induced by injection of streptozotocin in 6-week-old apoE-deficient mice. Diabetic animals received treatment with perindopril (4 mg x kg(-1) x d(-1)) or no treatment for 20 weeks. Nondiabetic apoE-deficient mice were used as controls. Induction of diabetes was associated with a 4-fold increase in plaque area compared with nondiabetic animals. This accelerated atherosclerosis was associated with a significant increase in aortic ACE expression and activity and connective tissue growth factor and vascular cell adhesion molecule-1 expression. Perindopril treatment inhibited the development of atherosclerotic lesions and diabetes-induced ACE, connective tissue growth factor, and vascular cell adhesion molecule-1 overexpression in the aorta.The activation of the local renin-angiotensin system in the diabetic aorta and the reduction in atherosclerosis with ACE inhibitor treatment provides further evidence that the renin-angiotensin system plays a pivotal role in the development and acceleration of atherosclerosis in diabetes. | Gov't Doc #: | 12105166 | URI: | http://ahro.austin.org.au/austinjspui/handle/1/9411 | Journal: | Circulation | URL: | https://pubmed.ncbi.nlm.nih.gov/12105166 | Type: | Journal Article | Subjects: | Actins.analysis Angiotensin-Converting Enzyme Inhibitors.therapeutic use Animals Aorta.chemistry.metabolism.pathology Apolipoproteins E.genetics Arteriosclerosis.etiology.metabolism.pathology.prevention & control Collagen.analysis Connective Tissue Growth Factor Diabetes Mellitus, Experimental.complications Disease Progression Growth Substances.biosynthesis.genetics Immediate-Early Proteins.biosynthesis.genetics Intercellular Signaling Peptides and Proteins Male Mice Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular.chemistry Peptidyl-Dipeptidase A.genetics.metabolism Perindopril.therapeutic use Phagocytes.physiology Proliferating Cell Nuclear Antigen.analysis RNA, Messenger.biosynthesis Vascular Cell Adhesion Molecule-1.biosynthesis.genetics |
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