Differential effects of apolipoprotein E3 and E4 on markers of oxidative status in macrophages
Differential effects of apolipoprotein E3 and E4 on markers of oxidative status in macrophages
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DOI：
10.1017/s0007114507669219
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发表时间：
2007-05-01
影响因子：
3.6
通讯作者：
Rimbach, Gerald
中科院分区：
文献类型：
--
作者：
Jofre-Monseny, Laia;de Pascual-Teresa, Sonia;Rimbach, Gerald
ApoE由动脉粥样硬化斑块病变部位的巨噬细胞分泌，在那里它被认为独立于其对脂质代谢的影响而对动脉粥样硬化起保护作用。在apoE的三种常见亚型中，apoE 4与心血管疾病（CVD）的风险较高相关。体外研究表明，重组apoE可能以亚型依赖性方式（E2 > E3 > E4）发挥抗氧化剂的作用。巨噬细胞的氧化状态在动脉粥样硬化的过程中起着关键作用。在本研究中，在稳定转染的小鼠巨噬细胞（RAW 2647-apoE 3和apoE 4）中确定了apoE 3和apoE 4对几个氧化状态参数的可能的差异作用。在过氧化物激发后，在细胞毒性保护或细胞膜氧化方面没有观察到基因型之间的差异，并且在apoE 3与apoE 4巨噬细胞中的非酶抗氧化剂（谷胱甘肽和α-生育酚）中观察到适度的差异。重要的是，分泌apoE 4的细胞在基础条件下表现出膜氧化增加，并且在刺激后比apoE 3巨噬细胞产生更多的NO和超氧阴离子自由基。目前的数据表明，载脂蛋白E基因型影响巨噬细胞的氧化状态，这可能部分有助于在apoE 4携带者中观察到的较高的CVD风险。
ApoE is secreted by macrophages at the lesion site of the atherosclerotic plaque, where it is thought to play a protective role against atherosclerosis independently of its effects on lipid metabolism. Of the three common isoforms for apoE, apoE4 is associated with higher risk of cardiovascular disease (CVD). In vitro studies have shown that recombinant apoE may act as an antioxidant in an isoform-dependent manner (E2 > E3 > E4). The oxidative status of the macrophages plays a key role in the process of atherosclerosis. In the present study the possible differential actions of apoE3 and apoE4 on several parameters of oxidative status were determined in stably transfected murine macrophages (RAW 2647-apoE3 and apoE4). No differences between genotypes were observed after peroxide challenge in either protection against cytotoxicity or in cell membrane oxidation, and modest differences were observed in the non-enzymatic antioxidants (glutathione and a-tocopherol) in apoE3 v. apoE4 macrophages. Importantly, cells secreting apoE4 showed increased membrane oxidation under basal conditions, and produced more NO and superoxide anion radicals than the apoE3 macrophages after stimulation. The present data suggest that apoE genotype influences the oxidative status of macrophages, and this could partly contribute to the higher CVD risk observed in apoE4 carriers.