Apolipoprotein A-I mimetic peptides prevent atherosclerosis development and reduce plaque inflammation in a murine model of diabetes.
Apolipoprotein A-I mimetic peptides prevent atherosclerosis development and reduce plaque inflammation in a murine model of diabetes.
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作者：
Morgantini C;Imaizumi S;Grijalva V;Navab M;Fogelman AM;Reddy ST
确定载脂蛋白A-I（ApoA-I）模拟肽D-4F对既存糖尿病患者动脉粥样硬化发展的影响。我们使用链脲佐菌素诱导6周龄apoE−/−雌性小鼠高血糖。一半的糖尿病apoE−/−小鼠在饮用水中接受D-4F。10周后，测量血脂、血糖、胰岛素水平、动脉粥样硬化病变和病变巨噬细胞含量。与非糖尿病apoE −/−小鼠相比，糖尿病apoE−/−小鼠的病变面积增加了300%，血脂异常明显，血糖水平升高，血浆胰岛素水平降低。D-4F治疗的糖尿病apoE−/−小鼠整个主动脉的动脉粥样硬化病变显着减少（1.11 ± 0.73vs0.58 ± 0.44，P < 0.01）和主动脉根部（36，038 ± 18，467 μm2/切片vs. 17，998 ± 12，491 μm2/切片，P < 0.01）。与未治疗动物相比，D-4F治疗的糖尿病apoE−/−小鼠动脉粥样硬化病变中的巨噬细胞含量显著降低（78.03 ± 26.1 vs. 29.6 ± 15.2 P < 0.001，整个斑块的百分比）。两组之间的血糖、胰岛素、总胆固醇、HDL胆固醇和甘油三酯水平没有差异。与非糖尿病apoE −/−小鼠相比，糖尿病apoE−/−小鼠肝组织中花生四烯酸、PGE 2、PGD 2、15-HETE、12-HETE和13-HODE浓度显著升高，D-4F治疗后显著降低。我们的研究结果表明，口服D-4F可以预防预先存在的糖尿病小鼠动脉粥样硬化的发展，这与肝脏花生四烯酸和氧化脂肪酸水平的降低有关。
To determine the effect of the apolipoprotein A-I (ApoA-I) mimetic peptide, D-4F, on atherosclerosis development in a pre-existing diabetic condition. We induced hyperglycemia in 6-week-old apoE−/− female mice using streptozotocin. Half of the diabetic apoE−/− mice received D-4F in drinking water. Ten weeks later, plasma lipids, glucose, insulin levels, atherosclerotic lesions, and lesion macrophage content were measured. Diabetic apoE−/− mice developed ∼300% more lesion area, marked dyslipidemia, increased glucose levels, and reduced plasma insulin levels when compared with nondiabetic apoE−/− mice. Atherosclerotic lesions were significantly reduced in the D-4F–treated diabetic apoE−/− mice in whole aorta (1.11 ± 0.73 vs. 0.58 ± 0.44, percentage of whole aorta, P < 0.01) and in aortic roots (36,038 ± 18,467 μm2/section vs. 17,998 ± 12,491 μm2/section, P < 0.01) when compared with diabetic apoE−/− mice that did not receive D-4F. Macrophage content in atherosclerotic lesions from D-4F–treated diabetic apoE−/− mice was significantly reduced when compared with nontreated animals (78.03 ± 26.1 vs. 29.6 ± 15.2 P < 0.001, percentage of whole plaque). There were no differences in glucose, insulin, total cholesterol, HDL cholesterol, and triglyceride levels between the two groups. Arachidonic acid, PGE2, PGD2, 15-HETE, 12-HETE, and 13-HODE concentrations were significantly increased in the liver tissue of diabetic apoE−/− mice compared with nondiabetic apoE−/− mice and significantly reduced by D-4F treatment. Our results suggest that oral D-4F can prevent atherosclerosis development in pre-existing diabetic mice and this is associated with a reduction in hepatic arachidonic acid and oxidized fatty acid levels.
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影响因子：
37.8
作者：
Kruger, AL;Peterson, S;Abraham, NG
通讯作者：
Abraham, NG
DOI：
10.1124/jpet.107.119479
发表时间：
2007-08-01
影响因子：
3.5
作者：
Peterson, Stephen J.;Husney, Daniel;Abraham, Nader G.
通讯作者：
Abraham, Nader G.
影响因子：
4.8
作者：
Fluiter, K;Sattler, W;van Berkel, TJC
通讯作者：
van Berkel, TJC
影响因子：
37.8
作者：
Navab, M;Anantharamaiah, GM;Fogelman, AM
通讯作者：
Fogelman, AM
影响因子：
5.3
作者：
Maeda, Nobuyo;Johnson, Lance;Reddick, Robert
通讯作者：
Reddick, Robert