In vitro biomarker discovery for atherosclerosis by proteomics

In vitro biomarker discovery for atherosclerosis by proteomics
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DOI:
10.1074/mcp.m400160-mcp200
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发表时间:
2004-12-01
影响因子:
7
通讯作者:
Opiteck, GJ
Opiteck, GJ
中科院分区:
生物学1区
文献类型:
--
作者:
Fach, EM;Garulacan, LA;Opiteck, GJ

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本研究的目的是在体外鉴定一组易于处理的动脉粥样硬化蛋白质生物标志物候选物,然后优先考虑这些候选物,这些候选物最终可能被开发用于测量动脉粥样硬化病变的程度、进展、消退和稳定性。使用体外“泡沫细胞”模型进行了一项研究,该模型基于用氧化低密度脂蛋白(氧化 LDL)与低密度脂蛋白(LDL)刺激分化的 THP1 细胞进行比较。使用蛋白质组扫描技术对细胞上清液中所含的蛋白质进行分析,发现与 LDL 相比,经氧化 LDL 处理后,59 种蛋白质含量增加,57 种蛋白质没有统计学上可测量的差异,17 种蛋白质含量减少。从上调列表中,蛋白质根据其分析置信度及其与动脉粥样硬化途径的相关性进行优先排序。在丰度增加的组中,七个蛋白质家族特别令人感兴趣:脂肪酸结合蛋白、几丁质酶样酶、亲环蛋白、组织蛋白酶、蛋白聚糖、尿激酶型纤溶酶原激活剂受体和巨噬细胞清道夫受体。
The purpose of this study was to identify in vitro and then prioritize a tractable set of protein biomarker candidates of atherosclerosis that may eventually be developed to measure the extent, progression, regression, and stability of atherosclerotic lesions. A study was conducted using an in vitro "foam cell" model based on the stimulation of differentiated THP1 cells with oxidized low-density lipoprotein ( oxidized LDL) as compared with low-density lipoprotein ( LDL). Analysis of the proteins contained in the cell supernatant using proteome scanning technology identified 59 proteins as being increased, 57 with no statistically measurable difference, and 17 decreasing in abundance following treatment with oxidized LDL, as compared with LDL. From the up-regulated list, proteins were prioritized based on their analytical confidence as well as their relevance to atherosclerosis pathways. Within the group of increased abundance, seven families of proteins were of particular interest: fatty acid-binding proteins, chitinase-like enzymes, cyclophilins, cathepsins, proteoglycans, urokinase-type plasminogen activator receptor, and a macrophage scavenger receptor.