1. Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice
- Author
-
Anna C. Calkin, Mark E. Cooper, Terri J. Allen, Karen Sheehy, A Soro-Paavonen, Jiaze Li, Karin Jandeleit-Dahm, Anna M.D. Watson, Daniella Brasacchio, Audrey Koitka, Merlin C. Thomas, and S Rajan
- Subjects
Apolipoprotein E ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Angiotensin-Converting Enzyme Inhibitors ,Peptidyl-Dipeptidase A ,medicine.disease_cause ,Alagebrium ,Diabetes Mellitus, Experimental ,Lesion ,chemistry.chemical_compound ,Mice ,Apolipoproteins E ,Internal medicine ,Diabetes mellitus ,Tetrahydroisoquinolines ,Internal Medicine ,medicine ,Animals ,Mice, Knockout ,biology ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Quinapril ,Angiotensin-converting enzyme ,medicine.disease ,Atherosclerosis ,Immunohistochemistry ,Endocrinology ,chemistry ,biology.protein ,Pyridoxamine ,medicine.symptom ,business ,Oxidative stress ,medicine.drug - Abstract
Formation of AGEs is increased in the diabetic milieu, which contributes to accelerated atherogenesis. We studied whether delayed treatment with AGE-inhibiting compounds, alagebrium chloride and pyridoxamine dihydrochloride, affected established atherosclerosis in experimental diabetes in comparison with the angiotensin-converting enzyme inhibitor, quinapril. Streptozotocin-induced diabetic male Apoe −/− mice (n = 24 per group) received, by oral gavage, from week 10 to 20 of diabetes: no treatment; alagebrium (1 mg kg−1 day−1); pyridoxamine (1 g/l in drinking water); or quinapril (30 mg kg−1 day−1). Atherosclerotic lesion area (en face analysis) was evaluated for all groups. Delayed intervention with alagebrium decreased plaque area in the diabetic Apoe −/− mice compared with untreated mice (total plaque area: alagebrium 10.6 ± 1.6%, untreated, 15.1 ± 1.5%, p
- Published
- 2010