Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein.
Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein.
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DOI：
10.1155/2015/592594
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发表时间：
2015
影响因子：
5.3
通讯作者：
Tozuka M
中科院分区：
文献类型：
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作者：
Kameda T;Ohkawa R;Yano K;Usami Y;Miyazaki A;Matsuda K;Kawasaki K;Sugano M;Kubota T;Tozuka M
高密度脂蛋白（HDL）对动脉粥样硬化的发展具有保护作用;这些作用包括胆固醇逆向转运、抗氧化能力和抗炎。由动脉粥样硬化病变中的巨噬细胞分泌的髓过氧化物酶（MPO）产生载脂蛋白A-I（apoA-I）分子中的酪氨酰自由基，通过HDL中的酪氨酸-酪氨酸键诱导apoA-I/apoA-II异二聚体的形成。MPO氧化HDL的功能特性可为apoA-I/apoA-II异二聚体测量的意义提供有用的信息。如上所述，我们研究了MPO诱导的氧化对HDL抗动脉粥样硬化功能的影响。HDL的抗氧化能力，估计对硫酸铜诱导的LDL氧化的影响，MPO氧化后没有显着影响。HDL通过抑制脂多糖（LPS）诱导的人脐静脉内皮细胞的刺激，减少THP-1单核细胞的迁移。MPO-氧化的HDL也表现出抑制THP-1的趋化性，但抑制的程度显着减弱相比，完整的HDL。MPO处理不影响HDL从THP-1细胞来源的[3 H]-胆固醇负载巨噬细胞的胆固醇流出能力。MPO氧化对HDL抗动脉粥样硬化作用的主要影响是降低HDL的抗炎能力，提示apoA-I/apoA-II异源二聚体的测定可用于评价HDL的抗炎能力。
High-density lipoprotein (HDL) has protective effects against the development of atherosclerosis; these effects include reverse cholesterol transport, antioxidant ability, and anti-inflammation. Myeloperoxidase (MPO) secreted by macrophages in atherosclerotic lesions generates tyrosyl radicals in apolipoprotein A-I (apoA-I) molecules, inducing the formation of apoA-I/apoA-II heterodimers through the tyrosine-tyrosine bond in HDL. Functional characterization of HDL oxidized by MPO could provide useful information about the significance of apoA-I/apoA-II heterodimers measurement. We investigated the effects of MPO-induced oxidation on the antiatherogenic functions of HDL as described above. The antioxidant ability of HDL, estimated as the effect on LDL oxidation induced by copper sulfate, was not significantly affected after MPO oxidation. HDL reduced THP-1 monocyte migration by suppressing the stimulation of human umbilical vein endothelial cells induced by lipopolysaccharide (LPS). MPO-oxidized HDL also showed inhibition of THP-1 chemotaxis, but the extent of inhibition was significantly attenuated compared to intact HDL. MPO treatment did not affect the cholesterol efflux capacity of HDL from [3H]-cholesterol-laden macrophages derived from THP-1 cells. The principal effect of MPO oxidation on the antiatherogenic potential of HDL would be the reduction of anti-inflammatory ability, suggesting that measurement of apoA-I/apoA-II heterodimers might be useful to estimate anti-inflammatory ability of HDL.