Inhibition of Protein Kinase Cβ Ameliorates Impaired Angiogenesis in Type I Diabetic Mice Complicating Myocardial Infarction

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著者

    • IKEDA Akihiko
    • Department of Cardiovascular Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba
    • MATSUSHITA Shonosuke
    • Department of Cardiovascular Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba
    • SAKAKIBARA Yuzuru
    • Department of Cardiovascular Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba

抄録

<b><i>Background:</i></b> In recent studies, the inhibition of protein kinase C (PKC) β has been shown to improve diabetic vascular complications. However, the effect on angiogenesis in myocardial ischemia with diabetes mellitus (DM) is still unknown. <b><i>Methods and Results:</i></b> Mice were divided into 3 groups: control, DM and DM+PKC-I groups (n=8, respectively). In the DM and DM+PKC-I groups, diabetes was induced by streptozotocin (STZ) (1.5mg/body i.p.) for 5 days. Next, left anterior descending artery (LAD) ligation was performed in all groups. In the DM+PKC-I group, PKC β inhibitor (Cat. No. 539654; 10nmol/L) was administered from days 1 to 10. After 4 weeks of LAD ligation, the animals were killed. Microvascular density was significantly improved by PKC β inhibitor (control: 87.9±5.2/high-power field (HPF); DM: 51.4±6.9/HPF; PKC-I: 80.3±4.9/HPF; P<0.05). Expression of both vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), which was decreased in the DM group, were significantly improved by inhibition of PKC β [VEGF (DM: 0.36±0.11-fold and DM+PKC-I: 0.77±0.07-fold vs. control), eNOS (DM: 0.35±0.06-fold and DM+PKC-I: 0.73±0.08-fold vs. control); both P<0.05)]. <b><i>Conclusions:</i></b> Inhibition of PKC β ameliorated impaired angiogenesis by hyperglycemia in STZ-induced DM mice complicated by myocardial infarction. These results suggest a new possible indication of PKC β inhibitor for myocardial ischemia with DM. (<i>Circ J</i> 2012; <b>76:</b> 943-949)<br>

収録刊行物

  • Circulation journal : official journal of the Japanese Circulation Society

    Circulation journal : official journal of the Japanese Circulation Society 76(4), 943-949, 2012-03-25

    一般社団法人 日本循環器学会

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各種コード

  • NII論文ID(NAID)
    10030131452
  • NII書誌ID(NCID)
    AA11591968
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13469843
  • データ提供元
    CJP書誌  J-STAGE 
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