Vascular Remodeling Induced by Naturally Occurring Unsaturated Lysophosphatidic Acid In Vivo

DOI Web Site 被引用文献14件
  • Kenji Yoshida
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Wataru Nishida
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Ken’ichiro Hayashi
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Yasuyuki Ohkawa
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Akira Ogawa
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Junken Aoki
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Hiroyuki Arai
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.
  • Kenji Sobue
    From the Department of Neuroscience, Osaka University Graduate School of Medicine (D13) (W.N., K.H., Y.O., K.S.); the Department of Neurosurgery, Iwate Medical University School of Medicine (K.Y., A.O.); and the Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo (J.A., H.A.), Japan.

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> We previously identified unsaturated (16:1, 18:1, and 18:2) but not saturated (12:0, 14:0, 16:0, and 18:0) lysophosphatidic acids (LPAs) as potent factors for vascular smooth muscle cell (VSMC) dedifferentiation. Unsaturated LPAs strongly induce VSMC dedifferentiation via the coordinated activation of the extracellular signal–regulated kinase (ERK) and p38 mitogen–activated protein kinase (p38MAPK), resulting in the proliferation and migration of dedifferentiated VSMCs. Here, we investigated the effects of 18:1 and 18:0 LPAs (as representative unsaturated and saturated LPAs, respectively) on the vasculature in vivo. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> Rat common carotid arteries (CCAs) were treated transiently with 18:1 or 18:0 LPA and then examined by histological and biochemical analyses. The 18:1 but not 18:0 LPA potently induced vascular remodeling that was composed primarily of neointima. The incorporation of [ <jats:sup>3</jats:sup> H]18:1 LPA into the CCAs revealed that a sufficient amount of unmetabolized [ <jats:sup>3</jats:sup> H]18:1 LPA to induce VSMC dedifferentiation was present in the vascular wall. The 18:1 LPA–induced neointimal formation in vivo was also dependent on the coordinated activation of ERK and p38MAPK. Unlike balloon-injured CCAs, the 18:1 LPA–treated CCAs showed a histological similarity to human atherosclerotic arteries. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> This is the first report demonstrating a role for a naturally occurring unsaturated LPA in inducing vascular remodeling in vivo and provides a novel animal model for neointimal formation. </jats:p>

収録刊行物

  • Circulation

    Circulation 108 (14), 1746-1752, 2003-10-07

    Ovid Technologies (Wolters Kluwer Health)

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