Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice

Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice
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DOI:
10.1161/atvbaha.108.164723
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发表时间:
2009-01-01
影响因子:
8.7
通讯作者:
Itabe, Hiroyuki
Itabe, Hiroyuki
中科院分区:
医学1区
文献类型:
--
作者:
Kato, Rina;Mori, Chihiro;Itabe, Hiroyuki

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背景-血浆氧化低密度脂蛋白(OxLDL)水平是心血管疾病的风险标志物。在疾病进展前血浆OxLDL的行为还没有研究previous.Methods和Results-In这项研究中,我们开发了一种灵敏的ELISA检测小鼠循环OxLDL使用单克隆抗体,识别氧化磷脂酰胆碱和兔antimouse载脂蛋白B-48多克隆抗体的程序。将载脂蛋白E敲除小鼠以普通饲料喂养40周。油红O阳性病变在20周时逐渐发展,28周后病变覆盖的面积百分比急剧增加,到40周时占表面积的33.4%。在10周时,从每只小鼠分离LDL组分后测量的OxLDL水平为0.015ng/μ g LDL。它在20周龄时增加了3倍,然后在40周龄时下降到基础水平,这表明OxLDL在动脉粥样硬化病变发展之前出现。脂质过氧化产物的发生,丙烯醛和氧化磷脂酰胆碱,在主动脉组织中的免疫组化染色显示,早在10 weeks. Conclusion-这些结果表明,OxLDL可能参与动脉粥样硬化病变进展的早期阶段。(Arterioscler Thromb Vasc Biol.2009; 29:33-39.)
Background-Plasma level of oxidized low-density lipoprotein (OxLDL) is a risk marker for cardiovascular diseases. The behavior of plasma OxLDL before disease progression has not been studied previously.Methods and Results-In this study, we developed a sensitive ELISA procedure for detecting mouse circulating OxLDL using a monoclonal antibody that recognizes oxidized phosphatidylcholine and a rabbit antimouse apolipoprotein B-48 polyclonal antibody. Apolipoprotein E knockout mice were fed on a chow diet for 40 weeks. Oil red O-positive lesions developed gradually by 20 weeks, and the percentage area covered by the lesions increased dramatically after 28 weeks; it covers 33.4% of the surface area by 40 weeks. The OxLDL level, measured after LDL fraction was isolated from each mouse, at 10 weeks was 0.015 ng/mu g LDL. It increased 3-fold at 20 weeks of age and then decreased to the basal level by 40 weeks of age, suggesting that OxLDL appears before the development of atherosclerotic lesions. The occurrence of lipid peroxidation products, acrolein and oxidized phosphatidylcholines, in aortic tissue were revealed by immunohistochemical staining as early as 10 weeks.Conclusion-These results suggest that OxLDL might be involved in the early stages of progression of atherosclerotic lesions. (Arterioscler Thromb Vasc Biol. 2009; 29: 33-39.)