Department of Orthopaedics and Centre for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Centre for Orthopaedics and Trauma Surgery, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
Department of Pharmacy, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Stem Cells. 2015 Jun;33(6):1863-77. doi: 10.1002/stem.2005. Epub 2015 Apr 21.
Reduced tissue levels of endothelial progenitor cells (EPCs) and functional impairment of endothelium are frequently observed in patients with diabetes and cardiovascular disease. The vascular endothelium is specifically sensitive to oxidative stress, and this is one of the mechanisms that causes widespread endothelial dysfunction in most cardiovascular diseases and disorders. Hence attention has increasingly been paid to enhance mobilization and differentiation of EPCs for therapeutic purposes. The aim of this study was to investigate whether Icariin, a natural bioactive component known from traditional Chinese Medicine, can induce angiogenic differentiation and inhibit oxidative stress-induced cell dysfunction in bone marrow-derived EPCs (BM-EPCs), and, if so, through what mechanisms. We observed that treatment of BM-EPCs with Icariin significantly promoted cell migration and capillary tube formation, substantially abrogated hydrogen peroxide (H2 O2 )-induced apoptotic and autophagic programmed cell death that was linked to the reduced intracellular reactive oxygen species levels and restored mitochondrial membrane potential. Icariin downregulated endothelial nitric oxide synthase 3, as well as nicotinamide-adenine dinucleotide phosphate-oxidase expression upon H2 O2 induction. These antiapoptotic and antiautophagic effects of Icariin are possibly mediated by restoring the loss of mammalian target of rapamycin /p70S6K/4EBP1 phosphorylation as well as attenuation of ATF2 and ERK1/2 protein levels after H2 O2 treatment. In summary, favorable modulation of the angiogenesis and redox states in BM-EPCs make Icariin a promising proangiogenic agent both enhancing vasculogenesis and protecting against endothelial dysfunction.
内皮祖细胞 (EPCs) 的组织水平降低和内皮功能障碍在糖尿病和心血管疾病患者中经常观察到。血管内皮对氧化应激特别敏感，这是大多数心血管疾病和紊乱导致广泛内皮功能障碍的机制之一。因此，人们越来越关注增强 EPC 的动员和分化以达到治疗目的。本研究旨在探讨从传统中药中已知的天然生物活性成分淫羊藿苷是否能诱导骨髓源性 EPC（BM-EPC）的血管生成分化并抑制氧化应激诱导的细胞功能障碍，如果可以，其机制是什么。我们观察到，淫羊藿苷处理 BM-EPC 可显著促进细胞迁移和毛细血管形成，显著抑制过氧化氢 (H2O2) 诱导的凋亡和自噬程序性细胞死亡，这与细胞内活性氧水平降低和线粒体膜电位恢复有关。H2O2 诱导时，淫羊藿苷下调内皮型一氧化氮合酶 3 和烟酰胺腺嘌呤二核苷酸磷酸氧化酶的表达。淫羊藿苷的这种抗凋亡和抗自噬作用可能是通过恢复哺乳动物雷帕霉素靶蛋白 (mTOR)/p70S6K/4EBP1 磷酸化的丧失以及减轻 H2O2 处理后 ATF2 和 ERK1/2 蛋白水平来介导的。总之，淫羊藿苷对 BM-EPC 中血管生成和氧化还原状态的有利调节使其成为一种有前途的促血管生成剂，既能增强血管生成，又能保护内皮功能障碍。
