title: Icariin promotes angiogenic differentiation and prevents oxidative stress-induced autophagy in endothelial progenitor cells.
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 (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.
authors: 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.
authors: Yubo
authors: Y
authors: Tang
authors: 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.
authors: Angela
authors: A
authors: Jacobi
authors: 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.
authors: Corina
authors: C
authors: Vater
authors: Department of Burn surgery and Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors: Lijin
authors: L
authors: Zou
authors: Department of Spinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Xuenong
authors: X
authors: Zou
authors: 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.
authors: Maik
authors: M
authors: Stiehler
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005419:Flavonoids; D017382:Reactive Oxygen Species; C056599:icariin
keywords: Akt/mammalian target of rapamycin/4EBP1; Angiogenesis; Autophagy; Endothelial progenitor cell; Icariin; p38 MAPK/ATF2