VPO1 mediates oxidation of LDL and formation of foam cells.
VPO1 mediates oxidation of LDL and formation of foam cells.
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DOI：
10.18632/oncotarget.9193
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发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Cheng G
中科院分区：
文献类型：
--
作者：
Yang Y;Shi R;Cao Z;Zhang G;Cheng G
血管壁中氧化ldl的沉积是动脉粥样硬化发生的必要条件。低密度脂蛋白的氧化已归因于髓过氧化物酶作为其产生的强氧化剂。然而，动脉粥样硬化中LDL氧化和泡沫细胞形成的确切机制仍有待阐明。血管过氧化物酶-1 （Vascular peroxidase-1, VPO1）是一种新发现的含血红素的过氧化物酶，主要表达于心血管系统，并分泌到血液循环中。本研究评估了vpo1介导的LDL氧化及其在动脉粥样硬化中的作用。VPO1首次被证实与LDL结合。通过多种方法验证了vpo1介导的LDL中蛋白质和脂质氧化，包括免疫印迹分析、游离色氨酸测定、紫外吸收和硫代巴比妥酸测定。vpo1氧化LDL引起LDL在单核细胞样细胞中的积累，促进泡沫细胞的形成。给药炎症因子LPS或TNF-α诱导主动脉VPO1表达增加，血浆中VPO1分泌增加。TNF-α也促进主动脉壁vpo1氧化LDL的形成和保留。我们的数据表明，VPO1有助于血管壁中LDL的氧化和滞留，并形成泡沫细胞，表明VPO1是一种新的潜在动脉粥样硬化介质。
Deposition of oxidized-LDL in vascular walls is essential in the initiation of atherosclerosis. Oxidation of LDL has been attributed to myeloperoxidase as its generation of potent oxidants. However, the exact mechanism of LDL oxidation and foam cell formation in atherosclerosis remains to be elucidated. Vascular peroxidase-1 (VPO1), a newly-identified heme-containing peroxidase, is primarily expressed in cardiovascular systems, and secreted into the circulation. The present study evaluates VPO1-mediated LDL oxidation and its role in atherosclerosis. VPO1 was first demonstrated binding to LDL. VPO1-mediated oxidation of proteins and lipids in LDL was verified by a variety of methods including immunoblot analysis, free tryptophan assay, UV absorbance, and thiobarbituric acid assay. VPO1-oxidized LDL caused accumulation of LDL in monocyte-like cells and promoted formation of foam cells. Administration of inflammation factors, LPS or TNF-α, induced increasing expression of VPO1 in aorta and secretion to plasma. TNF-α also promoted formation and retention of VPO1-oxidized LDL in aortic walls. Our data suggest that VPO1 contributes to oxidation and retention of LDL in vessel walls, and formation foam cells, indicating VPO1 as a novel potential mediator of atherosclerosis.
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