Upregulation of pentraxin-3 in human endothelial cells after lysophosphatidic acid exposure
Upregulation of pentraxin-3 in human endothelial cells after lysophosphatidic acid exposure
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DOI：
10.1161/atvbaha.107.158642
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发表时间：
2008-03-01
影响因子：
8.7
通讯作者：
Raes, Martine
中科院分区：
文献类型：
--
作者：
Gustin, Cindy;Delaive, Edouard;Raes, Martine
目的-动脉粥样硬化形成中最早的事件似乎是内皮功能障碍。溶血磷脂酸 (LPA) 是氧化低密度脂蛋白 (oxLDL) 的主要生物活性脂质成分之一，可引起内皮细胞 (EC) 激活，从而开始分泌多种促炎多肽/蛋白质。本研究的目的是使用亚蛋白质组学方法更好地记录 LPA 的促动脉粥样硬化特性，该方法专注于 LPA 处理的 EC 的分泌组。方法和结果 - 使用 2D-DIGE 方法分析 LPA 处理的 EC 的分泌组。与对照细胞相比，在丰度显着变化的 20 个点中，我们通过质谱法鉴定出 pentraxin-3。在永生化和原代 EC 上，Pentraxin-3 的上调在 mRNA 和蛋白质水平上得到证实。在 LPA 受体拮抗剂存在的情况下，LPA 以及 oxLDL 诱导的 pentraxin-3 上调都会降低，并且很大程度上依赖于 NF kappa B 激活。最后，我们首次通过趋化试验证明了 pentraxin-3 对人 THP-1 单核细胞的趋化活性。结论 - 我们的研究结果支持 LPA 的促动脉粥样硬化作用，LPA 是一种由活化血小板产生的生物活性脂质，存在于 oxLDL 中，因为它增强 pentraxin-3 的分泌，从而有助于单核细胞在动脉粥样硬化病变中的积累。
Objective - The earliest event in atherogenesis appears to be endothelium dysfunction. Lysophosphatidic acid (LPA), one of the major bioactive lipid components of oxidized low-density lipoproteins (oxLDL), can cause the activation of endothelial cells (ECs), which start to secrete multiple proinflammatory polypeptides/proteins. The purpose of this study was to better document the proatherogenic properties of LPA using a subproteomic approach focused on the secretome of LPA-treated ECs.Methods and Results - The secretome of LPA-treated ECs was analyzed using the 2D-DIGE approach. Among the 20 spots displaying significant variations of abundance compared with the control cells, we identified pentraxin-3 by mass spectrometry. Pentraxin-3 upregulation was confirmed at the mRNA and protein level, both on immortalized and primary ECs. LPA- but also oxLDL-induced pentraxin-3 upregulation was reduced in the presence of an antagonist of the LPA- receptors and largely dependent on NF kappa B activation. Finally, we demonstrated, for the first time, the chemotactic activity of pentraxin-3 on human THP-1 monocytes by using a chemotaxis assay.Conclusions - Our findings favor the proatherogenic role of LPA, a bioactive lipid produced by activated platelets and present in oxLDL, because it enhances pentraxin-3 secretion that could contribute to the accumulation of monocytes in the atherosclerotic lesion.