High Concentrations of Uric Acid Inhibit Angiogenesis via Regulation of the Kruppel-Like Factor 2-Vascular Endothelial Growth Factor-A Axis by miR-92a

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  • Yu Shandong
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital Department of Cardiology, First Hospital, Peking University
  • Hong Quan
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Wang Yuanda
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Hou Kai
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Wang Liyuan
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Zhang Yang
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Fu Bo
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Zhou Yunan
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Zheng Wei
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Chen Xiangmei
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital
  • Wu Di
    State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital

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タイトル別名
  • High Concentrations of Uric Acid Inhibit Angiogenesis via Regulation of the Krüppel-Like Factor 2-Vascular Endothelial Growth Factor-A Axis by miR-92a

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Background:Angiogenesis is a critical component of many pathological conditions, and microRNAs (miRNAs) are indispensable in angiogenesis. It is unclear whether miRNAs regulate angiogenesis in the presence of high concentrations of uric acid (HUA), and the underlying mechanisms remain unknown.Methods and Results:It was found that HUA inhibited the angiogenic ability of endothelial cells. miRNA expression profiling was conducted using microarray assays in HUA-stimulated endothelial cells. Eighteen differentially expressed miRNAs were subjected to bioinformatic analyses. The results indicated that miR-92a was negatively regulated and was closely related to angiogenesis. Furthermore, the effects of miR-92a on HUA-stimulated endothelial cell angiogenesis and the underlying mechanisms were investigated in dual-luciferase reporter assays, electrophoretic mobility shift assays, immunoblot assays, and tube formation assays. It was determined that Krüppel-like factor 2 (KLF2) is a target gene of miR-92a, and KLF2 binds the vascular endothelial growth factor-A (VEGFA) promoter to inhibit its expression. miR-92a and VEGFA overexpression or KLF2 downregulation alleviates the HUA-mediated inhibition of angiogenesis in endothelial cells in vitro.Conclusions:This study reported that there is a novel pathway regulating angiogenesis under HUA conditions. In the presence of HUA, miR-92a downregulation increased KLF2 expression, subsequently inhibiting VEGFA, which resulted in decreased angiogenesis. Thus, this study reports a possible mechanism for cardiovascular injury caused by hyperuricemia and suggests that the miR-92a-KLF2-VEGFA axis may be a target for hyperuricemia treatment. (Circ J 2015; 79: 2487–2498)

収録刊行物

  • Circulation Journal

    Circulation Journal 79 (11), 2487-2498, 2015

    一般社団法人 日本循環器学会

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