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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
Journal: Circulation
Type: Journal Article
Subjects: Actins.analysis
Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Apolipoproteins E.genetics
Arteriosclerosis.etiology.metabolism.pathology.prevention & control
Connective Tissue Growth Factor
Diabetes Mellitus, Experimental.complications
Disease Progression
Growth Substances.biosynthesis.genetics
Immediate-Early Proteins.biosynthesis.genetics
Intercellular Signaling Peptides and Proteins
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular.chemistry
Peptidyl-Dipeptidase A.genetics.metabolism
Perindopril.therapeutic use
Proliferating Cell Nuclear Antigen.analysis
RNA, Messenger.biosynthesis
Vascular Cell Adhesion Molecule-1.biosynthesis.genetics
Appears in Collections:Journal articles

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