Efficient expression of the vascular endothelial growth factor gene in vitro and in vivo, using an adeno-associated virus vector

被引:41
作者
Byun, J
Heard, JM
Huh, JE
Park, SJ
Jung, EA
Jeong, JO
Gwon, HC
Kim, DK
机构
[1] Sungkyunkwan Univ, Sch Med, Mol Therapy Res Ctr, Samsung Med Ctr,Dept Med,Kangnam Ku, Seoul 135710, South Korea
[2] Samsung Biomed Res Inst, Clin Res Ctr, Seoul 135230, South Korea
[3] Inst Pasteur, Lab Retrovirus & Transfert Genet, F-75724 Paris, France
关键词
VEGF; AAV; ischemia; gene therapy; angiogenesis;
D O I
10.1006/jmcc.2000.1301
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Vascular endothelial growth factor (VEGF) has proven to be one of the most effective growth factors for therapeutic angiogenesis. The biological efficacy of the adeno-associated virus (AAV) vector has recently been demonstrated in muscle tissues, including the heart. Apart from these promising insights into VEGF and the AAV vector, studies on WEGF gene transfer using the AAV vector have been limited, Here, we evaluate AAV-mediated VEGF gene transfer, both in vitro and in vivo, using the AAV-mVEGF vector that contains cDNA for murine VEGF(120) within an HCMV-driven expression cassette. Transient transfection of AAV-mVEGF plasmid significantly increased mVEGF expression in 293T cells. The secreted VEGF in the conditioned medium had strong biological activity, as confirmed by the Miles' vascular permeability assay. Transduction of 293T and HeLa cells with AAV-mVEGF stock of high titer, that is essentially adenovirus-free, showed significantly increased mVEGF expression above that of AAV-eGFP-transduced cells. When human umbilical vein endothelial cells were transduced, a higher level of mVEGF expression, together with higher cell counts, was observed compared to AAV-eGFP-transduced cells. In vivo transduction of mouse tibialis anterior muscle resulted in an increased level of mVEGF expression, and higher capillary-to-myofibre ratio, 8 weeks post-transduction. In a rat hindlimb ischemia model, regional blood flow, as well as the capillary-to-myofibre ratio, was significantly increased at 4 weeks post-transduction. These findings demonstrate the efficient delivery of the VEGF gene using an AAV vector, which has implications for angiogenic gene therapy in ischemic diseases, (C) 2001 Academic Press.
引用
收藏
页码:295 / 305
页数:11
相关论文
共 50 条
  • [41] Adeno-associated virus mediated expression of human erythropoietin in vitro
    Diao, Y
    Xu, RA
    Wang, GJ
    Zhao, XC
    [J]. ACTA PHARMACOLOGICA SINICA, 2002, 23 (01) : 55 - 58
  • [42] Angiopoiesis and bone regeneration via co-expression of the hVEGF and hBMP genes from an adeno-associated viral vector in vitro and in vivo
    Zhang, Chen
    Wang, Kun-zheng
    Qiang, Hui
    Tang, Yi-lun
    Li, Qian
    Li, Miao
    Dang, Xiao-qian
    [J]. ACTA PHARMACOLOGICA SINICA, 2010, 31 (07) : 821 - 830
  • [43] Reduction of choroidal neovascularization in mice by adeno-associated virus-delivered anti-vascular endothelial growth factor short hairpin RNA
    Askou, Anne Louise
    Pournaras, Jean-Antoine C.
    Pihlmann, Maria
    Svalgaard, Jesper D.
    Arsenijevic, Yvan
    Kostic, Corinne
    Bek, Toke
    Dagnaes-Hansen, Frederik
    Mikkelsen, Jacob Giehm
    Jensen, Thomas Gryesten
    Corydon, Thomas J.
    [J]. JOURNAL OF GENE MEDICINE, 2012, 14 (11) : 632 - 641
  • [44] Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector
    McCown, TJ
    Xiao, X
    Li, J
    Breese, GR
    Samulski, RJ
    [J]. BRAIN RESEARCH, 1996, 713 (1-2) : 99 - 107
  • [45] Evaluation of recombinant adeno-associated virus as a gene transfer vector for the retina
    Grant, CA
    Ponnazhagan, S
    Wang, XS
    Srivastava, A
    Li, TS
    [J]. CURRENT EYE RESEARCH, 1997, 16 (09) : 949 - 956
  • [46] Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases
    Bera, Abesh
    Sen, Dwaipayan
    [J]. HEART FAILURE REVIEWS, 2017, 22 (06) : 795 - 823
  • [47] Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases
    Abesh Bera
    Dwaipayan Sen
    [J]. Heart Failure Reviews, 2017, 22 : 795 - 823
  • [48] Cotransfection of Vascular Endothelial Growth Factor-A and Platelet-Derived Growth Factor-B Via Recombinant Adeno-Associated Virus Resolves Chronic Ischemic Malperfusion Role of Vessel Maturation
    Kupatt, Christian
    Hinkel, Rabea
    Pfosser, Achim
    El-Aouni, Chiraz
    Wuchrer, Alexander
    Fritz, Andrea
    Globisch, Franziska
    Thormann, Michael
    Horstkotte, Jan
    Lebherz, Corinna
    Thein, Eckart
    Banfi, Andrea
    Boekstegers, Peter
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 56 (05) : 414 - 422
  • [49] Regulation of gene expression in adeno-associated virus vectors in the brain
    Haberman, RP
    McGown, TJ
    [J]. METHODS, 2002, 28 (02) : 219 - 226
  • [50] One year transgene expression with adeno-associated virus cardiac gene transfer
    Woo, YJ
    Zhang, JCL
    Taylor, MD
    Cohen, JE
    Hsu, VM
    Sweeney, HL
    [J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 2005, 100 (03) : 421 - 426