Oxidized Lipoprotein as a Major Vessel Cell Proliferator in Oxidized Human Serum.
Oxidized Lipoprotein as a Major Vessel Cell Proliferator in Oxidized Human Serum.
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DOI：
10.1371/journal.pone.0160530
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Noguchi N
中科院分区：
文献类型：
--
作者：
Saito Y;Noguchi N
氧化应激与动脉粥样硬化和癌症等多种疾病的发生相关，氧化生物分子已被确定为氧化应激的生物标志物；然而，所产生的氧化产物与促进疾病之间的详细分子关系尚未完全阐明。在本研究中，为了阐明血清氧化产物在血管细胞增殖中的作用（与动脉粥样硬化和癌症的发生有关），对氧化的人血清中的主要血管细胞增殖剂进行了研究。通过自由基暴露制备氧化的人血清，使用凝胶色谱分离，然后将每个级分添加到包括内皮细胞和平滑肌细胞在内的多种血管细胞中。研究发现，氧化人血清中的高分子量组分特异性诱导血管细胞增殖。该高分子量级分中含有氧化脂质，而在氧化脂蛋白缺乏的血清中未观察到细胞增殖活性。氧化低密度脂蛋白以浓度依赖性方式诱导血管细胞增殖。总而言之，这些结果表明，含有脂质氧化产物的氧化脂蛋白在氧化人血清中起到主要血管细胞增殖剂的作用。这些发现强烈表明氧化脂蛋白和脂质氧化产物的测定在诊断血管细胞增殖相关疾病（例如动脉粥样硬化和癌症）中的相关性。
Oxidative stress is correlated with the incidence of several diseases such as atherosclerosis and cancer, and oxidized biomolecules have been determined as biomarkers of oxidative stress; however, the detailed molecular relationship between generated oxidation products and the promotion of diseases has not been fully elucidated. In the present study, to clarify the role of serum oxidation products in vessel cell proliferation, which is related to the incidence of atherosclerosis and cancer, the major vessel cell proliferator in oxidized human serum was investigated. Oxidized human serum was prepared by free radical exposure, separated using gel chromatography, and then each fraction was added to several kinds of vessel cells including endothelial cells and smooth muscle cells. It was found that a high molecular weight fraction in oxidized human serum specifically induced vessel cell proliferation. Oxidized lipids were contained in this high molecular weight fraction, while cell proliferation activity was not observed in oxidized lipoprotein-deficient serum. Oxidized low-density lipoproteins induced vessel cell proliferation in a concentration-dependent manner. Taken together, these results indicate that oxidized lipoproteins containing lipid oxidation products function as a major vessel cell proliferator in oxidized human serum. These findings strongly indicate the relevance of determination of oxidized lipoproteins and lipid oxidation products in the diagnosis of vessel cell proliferation-related diseases such as atherosclerosis and cancer.