Details

Autor(en) / Beteiligte

• CANDIDO, Riccardo
• JANDELEIT-DAHM, Karin A
• ZEMIN CAO
• NESTEROFF, Stefan P
• BURNS, Wendy C
• TWIGG, Stephen M
• DILLEY, Rodney J
• COOPER, Mark E
• ALIEN, Terri J

Titel

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

Ist Teil von

• Circulation (New York, N.Y.), 2002-07, Vol.106 (2), p.246-253

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.