Prevention of accelerated atherosclerosis by angiotensin-converting enzyme inhibition in diabetic apolipoprotein E-deficient mice

Riccardo Candido, Karin A. Jandeleit-Dahm, Zemin Cao, Stefan P. Nesteroff, Wendy C. Burns, Stephen M. Twigg, Rodney J. Dilley, Mark E. Cooper, Terri J. Allen

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237 Citations (Scopus)

Abstract

Background - 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. Methods and Results - Diabetes was induced by injection of streptozotocin in 6-week-old apoE-deficient mice. Diabetic animals received treatment with perindopril (4 mg·kg-1·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. Conclusions - 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.

Original languageEnglish
Pages (from-to)246-253
Number of pages8
JournalCirculation
Volume106
Issue number2
DOIs
Publication statusPublished - 9 Jul 2002
Externally publishedYes

Keywords

  • Angiotensin
  • Atherosclerosis
  • Diabetes mellitus
  • Vessels

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