Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects
Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects
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DOI：
10.1161/01.atv.0000177813.99577.6b
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发表时间：
2005-09-01
影响因子：
8.7
通讯作者：
Allen, TJ
中科院分区：
文献类型：
--
作者：
Calkin, AC;Forbes, JM;Allen, TJ
目的-最近的研究表明噻唑烷二酮类药物在减轻动脉粥样硬化中的作用。然而，这些研究是在与胰岛素和葡萄糖水平降低相关的胰岛素抵抗动物模型中进行的。为了评估噻唑烷二酮的血管效应，而与其代谢效应无关，我们在胰岛素不足模型中观察了罗格列酮对糖尿病相关动脉粥样硬化的影响。方法和结果-对照组和糖尿病载脂蛋白E缺陷小鼠接受罗格列酮或安慰剂.糖尿病小鼠的斑块面积增加了3倍，罗格列酮可使其减弱。治疗和未治疗的糖尿病动物之间的葡萄糖、胰岛素或胆固醇水平无显著差异。罗格列酮减弱糖尿病小鼠中观察到的超氧化物产生的增加。在治疗的糖尿病小鼠中观察到胆固醇逆向转运标志物ABCA 1增加4倍。罗格列酮降低血管紧张素II受体基因的表达在控制和糖尿病小鼠，巨噬细胞的积累增加糖尿病小鼠与对照组相比，并衰减rosiglitazone.Conclusions -这些研究结果表明，过氧化物酶体增殖物激活受体-γ配体，如罗格列酮赋予血管保护独立的代谢控制的影响。这些抗动脉粥样硬化作用可能不仅在胰岛素抵抗/2型糖尿病中，而且在1型糖尿病中具有重要的临床分支。
Objectives - Recent studies have demonstrated a role for thiazolidinediones in attenuating atherosclerosis. However, these studies were performed in insulin-resistant animal models in association with reductions in insulin and glucose levels. To assess the vascular effects of thiazolidinediones, independent of their metabolic effects, we observed the effect of rosiglitazone on diabetes-associated atherosclerosis in a model of insulin insufficiency. Methods andResults - Control and diabetic apolipoprotein E - deficient mice received rosiglitazone or placebo. Diabetic mice demonstrated a 3-fold increase in plaque area, which was attenuated by rosiglitazone. There was no significant difference in glucose, insulin, or cholesterol levels between treated and untreated diabetic animals. Rosiglitazone attenuated the increase in superoxide production observed in diabetic mice. A 4-fold increase in the reverse cholesterol transport marker ABCA1 was observed in treated diabetic mice. Rosiglitazone reduced angiotensin II receptor gene expression in control and diabetic mice, and macrophage accumulation was increased in diabetic mice compared with controls and was attenuated by rosiglitazone.Conclusions - These findings suggest peroxisome proliferator-activated receptor-gamma ligands such as rosiglitazone confer vascular protection independent of their effects on metabolic control. These antiatherosclerotic effects may have important clinical ramifications not only in insulin resistance/type 2 diabetes and also in type 1 diabetes.