Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress
Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress
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DOI：
10.1093/cvr/cvq191
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发表时间：
2010-11-01
影响因子：
10.8
通讯作者：
Lerman, Amir
中科院分区：
文献类型：
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作者：
Bachar, Adi R.;Scheffer, Lea;Lerman, Amir
Humanin（HN）是一种由24个氨基酸组成的肽，已被证明对阿尔茨海默病引起的神经元细胞死亡具有抗凋亡功能。氧化应激的增加是导致这种细胞死亡的主要因素之一，在动脉粥样硬化的炎症过程中也起着重要作用。本研究通过免疫组化染色检测人乳内动脉（n = 5）、冠状动脉粥样硬化（n = 17）和大隐静脉（n = 3）的内皮细胞层中HN在血管壁中的表达，以验证HN在人血管壁中表达并可保护免受氧化应激的假设。HN mRNA在人主动脉内皮细胞（HAECs）中表达。在体外HAECs中测试HN对氧化应激的细胞保护作用。用0.1 μ M HN预处理可减少氧化低密度脂蛋白（Ox-LDL）诱导的（i）活性氧簇的形成50%，（ii）通过TUNEL染色确定的细胞凋亡接近50%，以及（iii）神经酰胺（参与细胞凋亡的脂质第二信使）的形成信号级联，本研究首次证实HN在人血管内皮细胞层中表达。外源性添加HN的内皮细胞培养物被证明是有效的抗氧化低密度脂蛋白诱导的细胞凋亡。这些发现表明HN可能在人类早期动脉粥样硬化中起作用并可能具有保护作用。
Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress.HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n = 5), atherosclerotic coronary arteries (n = 17), and sections of the greater saphenous vein (n = 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 mu M HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by similar to 50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by similar to 20%.The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans.