Icariin Promotes Angiogenic Differentiation and Prevents Oxidative Stress-Induced Autophagy in Endothelial Progenitor Cells

淫羊藿苷 血管生成 祖细胞 氧化应激 血管生成 生物 细胞生物学 内皮祖细胞 干细胞 内皮功能障碍 内皮干细胞 NADPH氧化酶 烟酰胺腺嘌呤二核苷酸磷酸 癌症研究 免疫学 药理学 内分泌学 生物化学 医学 氧化酶试验 病理 替代医学 体外
作者
Yubo Tang,Angela Jacobi,Corina Vater,Lijin Zou,Xuenong Zou,Maik Stiehler
出处
期刊:Stem Cells [Wiley]
卷期号:33 (6): 1863-1877 被引量:94
标识
DOI:10.1002/stem.2005
摘要

Abstract 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 (H2O2)-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 H2O2 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 H2O2 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. Stem Cells 2015;33:1863–1877
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