The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway
The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway
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DOI：
10.1016/j.yjmcc.2017.01.017
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发表时间：
2017-04-01
影响因子：
5
通讯作者：
Wang, Yan
中科院分区：
文献类型：
--
作者：
Liu, Donghui;Ding, Zhenzhen;Wang, Yan
载脂蛋白A-I（apoA-I）模拟肽具有许多抗动脉粥样硬化的特性。然而，与内皮保护作用相关的潜在机制仍然难以捉摸。在本研究中，使用了apoA-I模拟肽D-4F。增殖实验、创伤愈合实验和transwell迁移实验表明D-4F改善了ox-LDL导致的内皮细胞增殖和迁移，单核细胞粘附实验表明D-4F抑制了内皮细胞炎症。Caspase-3活化和TUNEL染色显示D-4F减少内皮细胞凋亡。血红素加氧酶-1（heme oxygenase-1，HO-1）是一种重要的抗氧化酶。Akt/AMPK/eNOS信号通路参与了D-4F诱导HO-1表达的过程。此外，eNOS（L-NAME）和HO-1（Znpp）抑制剂均可降低D-4F的抗氧化、促增殖和促迁移能力。此外，通过siRNA下调ATP结合盒转运体A1（ABCA 1），消除了Akt、AMPK和eNOS的激活，并减少了D-4F引发的HO-1的上调。D-4F还能促进C57 BL/6 J小鼠颈动脉损伤模型中损伤内膜的再内皮化。综上所述，这些发现表明D-4F可能是保护内皮细胞和预防心血管疾病（CVD）的有力候选者。(C)2017由Elsevier Ltd.出版
Apolipoprotein A-I (apoA-I) mimetic peptide exerts many anti-atherogenic properties. However, the underlying mechanisms related to the endothelial protective effects remain elusive. In this study, the apoA-I mimetic peptide, D-4F, was used. Proliferation assay, wound healing, and transwell migration experiments showed that D-4F improved the impaired endothelial proliferation and migration resulting from ox-LDL Endothelial adhesion molecules expression and monocyte adhesion assay demonstrated that D-4F inhibited endothelial inflammation. Caspase-3 activation and TUNEL stain indicated that D-4F reduced endothelial cell apoptosis. A pivotal antioxidant enzyme, heme oxygenase-1 (HO-1) was upregulated by D-4F. The Akt/AMPK/eNOS pathways were involved in the expression of HO-1 induced by D-4F. Moreover, the anti-oxidation, pro-proliferation, and pro migration capacities of D-4F were diminished by the inhibitors of both eNOS (L-NAME) and HO-1 (Znpp). Additionally, downregulation of ATP-binding cassette transporter Al (ABCA1) by siRNA abolished the activation of Akt, AMPK and eNOS, and reduced the upregulation of HO-1 triggered by D-4F. Furthermore, D-4F promoted the reendothelialization of injured intima in carotid artery injury model of C57BL/6J mice in vivo. In summary, these findings suggested that D-4F might be a powerful candidate in the protection of endothelial cells and the prevention of cardiovascular disease (CVD). (C) 2017 Published by Elsevier Ltd.