title: Propranolol inhibits angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell.
abstract: BACKGROUND
  Oral propranolol (PRN) has recently been shown to be highly effective for infantile hemangiomas (IHs), and is currently recommended as the first-line treatment of complicated IHs. However, the therapeutic mechanism(s) still remain unclear.
  
  
  METHODS
  In this study, we tested hemangioma-derived stem cells for expression of vascular endothelial growth factor (VEGF) in vitro and studied the inhibition of VEGF expression. We used PCR, Elisa, Western blotting and immunohistochemistry in vivo and in vitro trial.
  
  
  RESULTS
  The study demonstrated that application of PRN at a "normal" concentration equivalent to plasma concentration did not inhibit proliferation or promote apoptosis of hemangioma derived stem cells (HemSCs) isolated from IH patients. PRN suppressed expression of vascular endothelial growth factor (VEGF) and basic Fibroblast Growth Factor (bFGF) in HemSCs in vitro. Morphological, histological and immunohistological improvement were observed in vivo using murine IH model in which HemSCs pre-treated with PRN were implanted into BALB/c-nu mice. In the pre-treated HemSC grafts, mean micro-vessel density (MVD) significantly decreased and protein levels of VEGF markedly decreased, while bFGF was still detectable.
  
  
  CONCLUSIONS
  The results suggested PRN inhibited angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell. These findings provide critical insight into the potential mechanisms of PRN action on IH.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, China ; Department of Oral and Maxillofacial Surgery, College of Stomatology, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Hua-Ming
authors.initials: HM
authors.lastname: Mai
authors.affiliation: Laboratory of Molecular Neuropharmacology, School of Pharmacy East China, University of Science and Technology 130 Meilong Road, Shanghai 200237, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Zheng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, China.
authors.forename: Yan-An
authors.initials: YA
authors.lastname: Wang
authors.affiliation: Special Department of Vascular Anomalies, Linyi Tumor Hospital Linyi 276000, Shandong Province, China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Qin
authors.affiliation: Special Department of Vascular Anomalies, Linyi Tumor Hospital Linyi 276000, Shandong Province, China.
authors.forename: Ke-Lei
authors.initials: KL
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006391:Hemangioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D011433:Propranolol
keywords: Hemangioma-stem cell; pharmacokinetics; propranolol; vascular endothelial growth factor (VEGF)