Apolipoproteins A-IV and A-V are acute-phase proteins in mouse HDL
Apolipoproteins A-IV and A-V are acute-phase proteins in mouse HDL
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DOI：
10.1016/j.atherosclerosis.2004.04.018
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发表时间：
2004-09-01
期刊：
影响因子：
5.3
通讯作者：
Feingold, KR
中科院分区：
文献类型：
--
作者：
Khovidhunkit, W;Duchateau, PN;Feingold, KR
背景：感染和炎症与动脉粥样硬化有关。在感染和炎症期间，HDL降低，并且几种HDL相关蛋白的水平发生变化。为了鉴定感染和炎症期间HDL的蛋白质组成的变化，利用蛋白质组学方法。方法和结果：使用二维凝胶电泳和质谱，我们发现载脂蛋白（apo）SAA和apo E的预期增加。以及从注射内毒素的小鼠中分离的HDL上的载脂蛋白A-I降低。我们确定载脂蛋白A-IV和载脂蛋白AN为小鼠HDL中的阳性急性时相蛋白。我们还发现，在注射内毒素后，肝脏载脂蛋白A-IV和载脂蛋白AN的mRNA水平增加。白细胞介素-6增加Hep 3B细胞中apo A-IV和apo AN mRNA水平。此外，我们还证实了急性期HDL中载脂蛋白A-II的蛋白水平和载脂蛋白A-II的肝脏mRNA水平降低。结论：载脂蛋白A-IV和AN是阳性急性时相蛋白，在炎症期间血清中增加，而载脂蛋白A-II是小鼠中的阴性急性时相蛋白。与其他阳性和阴性急性时相蛋白类似，肝脏产生的变化可解释血清水平的变化。然而，载脂蛋白A-IV和载脂蛋白AN的变化，其活性尚未完全了解，可能在急性相反应（APR）期间发挥调节脂质代谢以外的功能。再加上HDL蛋白发生的其他变化，这些变化可能会改变HDL的功能特性，可能会增加动脉粥样硬化的风险。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Background: Infection and inflammation are associated with atherosclerosis. During infection and inflammation, HDL decreases and there are changes in the levels of several HDL-associated proteins. To identify changes in the protein composition of HDL during infection and inflammation, a proteomic approach was utilized. Methods and results: Using two-dimensional gel electrophoresis and mass spectrometry, we found the expected increases in apolipoprotein (apo) SAA and apo E. as well as a decrease in apo A-I on HDL isolated from mice injected with endotoxin. We identified apo A-IV and apo AN as positive acute-phase proteins in mouse HDL. We also found an increase in hepatic mRNA levels of apo A-IV and apo AN after injection of endotoxin. Interleukin-6 increased apo A-IV and apo AN mRNA levels in Hep3B cells. Additionally, we demonstrated that the protein levels of apo A-II in acute-phase HDL and the hepatic mRNA levels of apo A-II were decreased. Conclusions: Apo A-IV and AN are positive acute-phase proteins that increase in the serum during inflammation while apo A-II is a negative acute-phase protein in mice. Similar to other positive and negative acute-phase proteins, changes in hepatic production account for the changes in serum levels. However, the changes in apo A-IV and apo AN, two apolipoproteins whose activities are not fully understood, may serve functions other than regulating lipid metabolism during the acute-phase response (APR). Coupled with the other changes in HDL proteins that occur, these changes are likely to alter the functional properties of HDL perhaps increasing the risk of atherosclerosis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.