Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice

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