Adiponectin receptor 2 deficiency results in reduced atherosclerosis in the brachiocephalic artery in apolipoprotein E deficient mice.

Adiponectin receptor 2 deficiency results in reduced atherosclerosis in the brachiocephalic artery in apolipoprotein E deficient mice.
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DOI:
10.1371/journal.pone.0080330
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Lindén D
Lindén D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lindgren A;Levin M;Rodrigo Blomqvist S;Wikström J;Ahnmark A;Mogensen C;Böttcher G;Bohlooly-Y M;Borén J;Gan LM;Lindén D

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脂联素已被证明具有有益的心血管作用,并通过脂联素受体AdipoR 1和AdipoR 2发出信号。本研究的最初目的是研究AdipoR 1和AdipoR 2联合缺乏(AdipoR 1-/-AdipoR 2-/-)对动脉粥样硬化的影响。然而,我们做了有趣的观察,AdipoR 1-/-AdipoR 2-/-导致胚胎死亡,证明了脂联素信号系统在发育过程中的至关重要性。然后,我们研究了AdipoR 2消融对载脂蛋白E缺陷(ApoE -/-)小鼠动脉粥样硬化进展的影响。与AdipoR 2 +/+ ApoE-/-同窝对照组相比,喂食致动脉粥样硬化饮食的AdipoR 2-/-ApoE-/-小鼠头臂动脉中的斑块面积减少,如使用超声生物显微镜在体内可视化的,并通过组织学分析证实。头臂动脉斑块面积的减少不能用血浆胆固醇水平或炎症状态来解释。然而,与氧化LDL孵育后,AdipoR 2-/-ApoE-/-小鼠腹腔巨噬细胞中中性脂质的蓄积减少。与氧化LDL孵育后的AdipoR 2 +/+ApoE-/-对照相比,该效应与AdipoR 2-/-ApoE-/-小鼠腹腔巨噬细胞中较低的CD 36和较高的ABCA 1 mRNA水平相关。总之,我们发现脂联素受体在胚胎发育过程中是至关重要的,并且AdipoR 2缺陷减缓了ApoE缺陷小鼠头臂动脉粥样硬化的进展。
Adiponectin has been shown to have beneficial cardiovascular effects and to signal through the adiponectin receptors, AdipoR1 and AdipoR2. The original aim of this study was to investigate the effect of combined AdipoR1 and AdipoR2 deficiency (AdipoR1-/-AdipoR2-/-) on atherosclerosis. However, we made the interesting observation that AdipoR1 -/- AdipoR2 -/- leads to embryonic lethality demonstrating the critical importance of the adiponectin signalling system during development. We then investigated the effect of AdipoR2-ablation on the progression of atherosclerosis in apolipoprotein E deficient (ApoE -/-) mice. AdipoR2-/-ApoE-/- mice fed an atherogenic diet had decreased plaque area in the brachiocephalic artery compared with AdipoR2 +/+ApoE-/- littermate controls as visualized in vivo using an ultrasound biomicroscope and confirmed by histological analyses. The decreased plaque area in the brachiocephalic artery could not be explained by plasma cholesterol levels or inflammatory status. However, accumulation of neutral lipids was decreased in peritoneal macrophages from AdipoR2-/-ApoE-/- mice after incubation with oxidized LDL. This effect was associated with lower CD36 and higher ABCA1 mRNA levels in peritoneal macrophages from AdipoR2-/-ApoE-/- mice compared with AdipoR2+/+ApoE-/- controls after incubation with oxidized LDL. In summary, we show that adiponectin receptors are crucial during embryonic development and that AdipoR2-deficiency slows down the progression of atherosclerosis in the brachiocephalic artery of ApoE-deficient mice.
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发表时间: 2010-06
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发表时间: 1994-01-01
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发表时间: 2000-04-01
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