Lack of association between adiponectin levels and atherosclerosis in mice.
Lack of association between adiponectin levels and atherosclerosis in mice.
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DOI：
10.1161/atvbaha.109.195826
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Scherer PE
中科院分区：
文献类型：
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作者：
Nawrocki AR;Hofmann SM;Teupser D;Basford JE;Durand JL;Jelicks LA;Woo CW;Kuriakose G;Factor SM;Tanowitz HB;Hui DY;Tabas I;Scherer PE
脂联素是一种脂肪细胞来源的分泌蛋白，参与保护机体免受一系列相关代谢紊乱的影响。缺乏脂联素的小鼠表现出肝脏胰岛素敏感性受损，并且仅对PPARγ激动剂有部分反应。脂联素具有抗炎和抗动脉粥样硬化的特性，然而，脂联素对动脉粥样硬化过程的直接参与尚未研究。我们将脂联素敲除小鼠（Adn−/−）或脂联素水平长期升高的小鼠（AdnTg）与低密度脂蛋白受体缺失（Ldlr−/−）和载脂蛋白E缺失（Apoe−/−）小鼠模型杂交。脂联素水平与动脉粥样硬化过程的抑制无关。在各种饮食条件下，主动脉根部的斑块体积、主动脉中的胆固醇积聚和斑块形态不受循环脂联素水平的影响。鉴于脂联素与人类心血管疾病的强相关性，在小鼠功能获得和丧失研究中缺乏表型可能表明脂联素抑制动脉粥样硬化病变形成缺乏因果关系。这些数据表明，脂联素对心血管系统的作用是复杂和多方面的，在临床前啮齿动物模型中对动脉粥样硬化斑块形成的直接影响最小。
Adiponectin is an adipocyte-derived, secreted protein that is implicated in the protection against a cluster of related metabolic disorders. Mice lacking adiponectin display impaired hepatic insulin sensitivity and respond only partially to PPARγ agonists. Adiponectin has been associated with anti-inflammatory and anti-atherogenic properties, however, the direct involvement of adiponectin on the atherogenic process has not been studied. We crossed adiponectin knockout mice (Adn−/−) or mice with chronically elevated adiponectin levels (AdnTg) into the low-density lipoprotein receptor null (Ldlr−/−) and the apoliprotein E null (Apoe−/−) mouse models. Adiponectin levels did not correlate with a suppression of the atherogenic process. Plaque volume in the aortic root, cholesterol accumulation in the aorta and plaque morphology under various dietary conditions were not affected by circulating adiponectin levels. In light of the strong associations reported for adiponectin with cardiovascular disease in humans, the lack of a phenotype in gain- and loss-of-function studies in mice may suggests lack of causation for adiponectin in inhibiting the build up of atherosclerotic lesions. These data indicate that the actions of adiponectin on the cardiovascular system are complex and multifaceted, with a minimal direct impact on atherosclerotic plaque formation in preclinical rodent models.