Effects of apolipoprotein M in uremic atherosclerosis
Effects of apolipoprotein M in uremic atherosclerosis
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DOI：
10.1016/j.atherosclerosis.2017.08.005
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发表时间：
2017-10-01
期刊：
影响因子：
5.3
通讯作者：
Pedersen, Tanja Xenia
中科院分区：
文献类型：
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作者：
Bosteen, Markus Hoybye;Svarrer, Eva Martha Madsen;Pedersen, Tanja Xenia
背景和目的：慢性肾脏疾病的特征是尿毒症，并导致过早死亡，部分原因是动脉粥样硬化加速。载脂蛋白（apo）M是脂质鞘氨醇-1-磷酸（S1 P）的血浆载体蛋白。Apom-S1 P复合物与HDL相关，并可能有助于其抗动脉粥样硬化作用。Apom/S1 P在动脉粥样硬化中的作用目前存在争议，并且尚未在尿毒症环境中进行探索。我们的目的是探讨血浆中Apom/S1 P的浓度是否会改变尿毒症和Apom的过度表达或缺乏是否会影响经典和尿毒症atherosclerosis.Methods：轻度至中度尿毒症诱导次全肾切除术（NX）在86-92 ApoE缺陷小鼠，Apom野生型，Apom缺陷，或Apom过度表达（类似10倍）。尿毒症对血浆Apom/S1 P和动脉粥样硬化的影响进行了评估，并与非肾切除controls.Results：尿毒症增加血浆Apom相似的25%，但不是S1 P。血浆S1 P在过表达Apom的小鼠中升高约300%，在Apom缺陷小鼠中降低约25%。Apom过表达增加主动脉根部动脉粥样硬化和血浆胆固醇。相反，主动脉弓动脉粥样硬化不受Apom基因型的影响。Apom缺乏或Apom过度表达对尿毒症atherosclerosis.Conclusions：这项研究强调了Apom/S1 P在动脉粥样硬化中的复杂性，并挑战了Apom/S1 P复合物是抗动脉粥样硬化的概念，至少在ApoE缺乏的小鼠中。(C)2017爱思唯尔B. V.保留所有权利。
Background and aims: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute to its anti-atherosclerotic effects. The role of Apom/S1P in atherosclerosis is presently controversial and has not been explored in a uremic setting. We aimed to explore whether plasma concentrations of Apom/S1P are altered by uremia and whether Apom overexpression or deficiency affects classical and uremic atherosclerosis.Methods: Mild to moderate uremia was induced by subtotal nephrectomy (NX) in 86-92 Apoe-deficient mice that were either Apom-wild type, Apom-deficient, or overexpressed Apom (similar to 10 fold). The effects of uremia on plasma Apom/S1P and atherosclerosis were evaluated and compared to non-nephrectomized controls.Results: Uremia increased plasma Apom by similar to 25%, but not S1P. Plasma S1P was elevated by similar to 300% in mice overexpressing Apom, and decreased by similar to 25% in Apom-deficient mice. Apom overexpression augmented aortic root atherosclerosis and plasma cholesterol. In contrast, aortic arch atherosclerosis was unaffected by the Apom genotype. There was no effect of Apom-deficiency or Apom overexpression on uremic atherosclerosis.Conclusions: This study highlights the complexity of Apom/S1P in atherosclerosis and challenges the notion that the Apom/S1P complex is anti-atherogenic, at least in Apoe-deficient mice. (C) 2017 Elsevier B.V. All rights reserved.