Chronic treatment with sulfhydryl angiotensin-converting enzyme inhibitors reduce susceptibility of plasma LDL to in vitro oxidation, formation of oxidation-specific epitopes in the arterial wall, and atherogenesis in apolipoprotein E knockout mice

• Published in: International journal of cardiology 2001-12, Vol.81 (2), p.107-115
• Main Authors: de Nigris, F, D’Armiento, F.P, Somma, P, Casini, A, Andreini, I, Sarlo, F, Mansueto, G, De Rosa, G, Bonaduce, D, Condorelli, M, Napoli, C
• Format: Article
• Language: English
• Subjects: Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Aortic Valve Stenosis - drug therapy; Aortic Valve Stenosis - etiology; Aortic Valve Stenosis - metabolism; Apolipoprotein E-deficient mice; Apolipoproteins E - drug effects; Arteries - chemistry; Arteries - drug effects; Arteriosclerosis - drug therapy; Arteriosclerosis - immunology; Arteriosclerosis - metabolism; Atherosclerosis; Blood Pressure - drug effects; Captopril - administration & dosage; Captopril - analogs & derivatives; Captopril - antagonists & inhibitors; Captopril - therapeutic use; Cholesterol - blood; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril - therapeutic use; Epitopes - metabolism; Immunohistochemistry; LDL; Lipid Peroxidation - drug effects; Lipoproteins, LDL - blood; Lipoproteins, LDL - immunology; Lipoproteins, LDL - metabolism; Male; Mice; Mice, Knockout; Oxidation; Oxidation-Reduction; Oxidative Stress - drug effects; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - drug effects; Random Allocation; Sulfhydryl Reagents - therapeutic use; Time Factors; Treatment Outcome
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/S0167-5273(01)00542-3

The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE −/−) mice. Groups of 2-month-old male mice received either placebo ( N=10), 0.05 mg/kg/day of zofenopril ( N=10), 1 mg/kg/day of zofenopril ( N=10), 5 mg/kg/day of captopril ( N=10) or 0.5 mg/kg/day of enalapril ( N=8). After 29 weeks of treatment, computer-assisted imaging analysis revealed that zofenopril reduced the aortic cumulative lesion area by 78% at 0.05 mg/kg/day and by 89% at 1 mg/ml/day of zofenopril compared to that of the placebo ( P