Blockade of Vascular Endothelial Growth Factor Suppresses Experimental Restenosis After Intraluminal Injury by Inhibiting Recruitment of Monocyte Lineage Cells

  • Kisho Ohtani
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Kensuke Egashira
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Ken-ichi Hiasa
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Qingwei Zhao
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Shiro Kitamoto
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Minako Ishibashi
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Makoto Usui
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Shujiro Inoue
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Yoshikazu Yonemitsu
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Katsuo Sueishi
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Masataka Sata
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Masabumi Shibuya
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Kenji Sunagawa
    From the Departments of Cardiovascular Medicine (K.O., K.E., M.U., Q.Z., S.K., M.I., K.-i.H., S.I., K.S.) and Pathology (Y.Y., S.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; the Department of Cardiovascular Medicine (M. Sata), Graduate School of Medical Sciences, University of Tokyo, Tokyo; and the Division of Genetics (M. Shibuya), Institute of Medical Science, University of Tokyo, Tokyo, Japan.

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> We report herein that blockade of VEGF by soluble VEGF receptor 1 ( <jats:italic>sFlt-1</jats:italic> ) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice. <jats:italic>sFlt-1</jats:italic> gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation. <jats:italic>sFlt-1</jats:italic> gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monocyte-lineage cells. </jats:p>

収録刊行物

  • Circulation

    Circulation 110 (16), 2444-2452, 2004-10-19

    Ovid Technologies (Wolters Kluwer Health)

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