Angiogenesis and Vasculogenesis Are Impaired in the Precocious-Aging <i>klotho</i> Mouse

DOI Web Site 被引用文献12件
  • Toshifumi Shimada
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Yoshiaki Takeshita
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Toyoaki Murohara
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Ken-ichiro Sasaki
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Kimiyasu Egami
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Satoshi Shintani
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Yosuke Katsuda
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Hisao Ikeda
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Yo-ichi Nabeshima
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Tsutomu Imaizumi
    From the Cardiovascular Research Institute (T.S., Y.T., T.M., K.-i.S., K.E., S.S., Y.K., H.I., T.I.), Kurume University, Kurume; the Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine, Nagoya; and the Department of Pathology and Tumor Biology (Y.-i.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> The effects of aging on angiogenesis (vascular sprouting) and vasculogenesis (endothelial precursor cell [EPC] incorporation into vessels) are not well known. We examined whether ischemia-induced angiogenesis/vasculogenesis is altered in <jats:italic>klotho</jats:italic> ( <jats:italic>kl</jats:italic> ) mutant mice, an animal model of typical aging. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> After unilateral hindlimb ischemia, laser Doppler blood-flow (LDBF) analysis revealed a decreased ischemic-normal LDBF ratio in <jats:italic>kl</jats:italic> mice. Tissue capillary density was also suppressed in <jats:italic>kl</jats:italic> mice ( <jats:italic>+/+</jats:italic> > <jats:italic>+/kl</jats:italic> > <jats:italic>kl/kl</jats:italic> ). Aortic-ring culture assay showed impaired angiogenesis in <jats:italic>kl/kl</jats:italic> mice, accompanied by reduced endothelium-derived nitric oxide release. Moreover, the rate of transplanted homologous bone marrow cells incorporated into capillaries in ischemic tissues (vasculogenesis) was lower in <jats:italic>kl/kl</jats:italic> mice than in wild-type ( <jats:italic>+/+</jats:italic> ) mice, which was associated with a decrease in the number of c-Kit <jats:sup>+</jats:sup> CD31 <jats:sup>+</jats:sup> EPC-like mononuclear cells in bone marrow and in peripheral blood. Finally, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin restored the impaired neovascularization in <jats:italic>kl/kl</jats:italic> mice, accompanied by an increase in c-Kit <jats:sup>+</jats:sup> CD31 <jats:sup>+</jats:sup> cells in bone marrow and peripheral blood, and enhanced angiogenesis in the aortic-ring culture. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Angiogenesis and vasculogenesis are impaired in <jats:italic>kl</jats:italic> mutant mice, a model of typical aging. Moreover, the age-associated impairment of neovascularization might be a new target of statin therapy. </jats:p>

収録刊行物

  • Circulation

    Circulation 110 (9), 1148-1155, 2004-08-31

    Ovid Technologies (Wolters Kluwer Health)

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