| First Author | Watson AM | Year | 2011 |
| Journal | Diabetologia | Volume | 54 |
| Issue | 3 | Pages | 681-9 |
| PubMed ID | 21161164 | Mgi Jnum | J:170363 |
| Mgi Id | MGI:4946362 | Doi | 10.1007/s00125-010-2000-9 |
| Citation | Watson AM, et al. (2011) Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice. Diabetologia 54(3):681-9 |
| abstractText | AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 < 0.05). This anti-atherosclerotic effect was comparable with that achieved with quinapril (quinapril 8.4 +/- 1.4%, vs untreated, p < 0.05). Pyridoxamine also attenuated plaque development in diabetic mice (5.7 +/- 1.2% vs untreated 11.9 +/- 1.1%, p < 0.05). The anti-atherosclerotic effect conferred by alagebrium and quinapril was associated with a significant reduction in vascular oxidative stress and circulating AGEs and methylglyoxal, although preformed AGEs were not removed from the vascular wall with either delayed intervention. CONCLUSIONS/INTERPRETATION: Inhibition of AGE accumulation, using a delayed intervention with alagebrium or pyridoxamine, significantly attenuated the progression of established diabetes-associated atherosclerosis, similar to results obtained with quinapril. These findings provide further evidence that blockade of AGE-mediated pathways may present a novel therapy for the prevention of atherosclerosis in diabetes. |
