Increased Production of Vascular Endothelial Growth Factor-D and Lymphangiogenesis in Acute Kawasaki Disease

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概要

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• Background: Kawasaki disease (KD) is characterized by systemic vasculitis with tissue edema. During the healing process of inflammation, lymphangiogenesis is essential for reducing tissue edema. One potential responsible candidate for the induction of lymphangiogenesis in the healing process of acute KD is vascular endothelial growth factor-D (VEGF-D). Methods and Results: Sequential changes in serum VEGF-D levels in patients with acute KD (n=47) using an enzyme-linked immunosorbent assay were investigated. Cross-sectional areas of lymphatic vessels and VEGF-D protein expression were evaluated immunohistochemically in cardiac tissues of patients (n=6) who died of KD. Regulation of VEGF-D messenger RNA (mRNA) expression in cultured fibroblasts was assessed using quantitative real-time polymerase chain reaction. Serum VEGF-D levels increased after intravenous immunoglobulin therapy in patients with acute KD (P<0.001). In addition, they were significantly lower in patients with coronary artery lesions (CAL) than in those without CAL (P<0.05). The cross-sectional areas of lymphatic vessels in cardiac tissues were enlarged in patients with acute KD. VEGF-D protein was detected on the endothelium of the enlarged lymphatic vessels. In vitro, tumor necrosis factor- significantly down-regulated VEGF-D mRNA expression in cultured fibroblasts (P=0.004). Conclusions: This study indicates that the production of VEGF-D increases and is related to lymphangiogenesis in patients with acute KD. In addition, low VEGF-D production appears to be associated with the development of CAL. (Circ J 2011; 75: 1455-1462)

• 2011-05-25

著者

• Saito Hirohisa

  Department Of Allergy And Immunology National Research Institute For Child Health And Development

• Saito Hirohisa

  Department Of Allergy & Immunology National Research Institute For Child Health And Development

• Kohno Yoichi

  Department Of Pediatrics Chiba University Graduate School Of Medicine

• Terai Masaru

  Tokyo Women's Med Univ

• Terai Masaru

  Department Of Pediatrics Chiba University School Of Medicine

• Terai Masaru

  Department Of Pediatrics Graduate School Of Medicine Chiba University

• Hamada Hiromichi

  Department Of Pediatrics Graduate School Of Medicine Chiba University

• Tajimi Morihiro

  Department Of Public Health Jichi Medical School

• Suwazono Yasushi

  Department Of Occupational And Environmental Medicine Graduate School Of Medicine Chiba University

• Higashi Kouji

  Department Of Pediatrics Graduate School Of Medicine Chiba University

• Higashi Kouji

  Department Of Electronics Miyazaki University

• YASUKAWA Kumi

  Department of Pediatrics, Chiba University School of Medicine

• Abe Jun

  Department Of Biology Faculty Of Science Kobe University

• EBATA Ryota

  Department of Pediatrics, Graduate School of Medicine, Chiba University

• Ebata Ryota

  Department Of Pediatrics Graduate School Of Medicine Chiba University

• Hamada Hiromichi

  Department Of Pediatrics Tokyo Women's Medical University Yachiyo Medical Center

• Yasukawa Kumi

  Department Of Pediatrics Graduate School Of Medicine Chiba University

• Yasukawa Kumi

  Department Of Pediatrics Chiba University School Of Medicine

• Abe Jun

  Department Of Allergy And Immunology National Research Institute For Child Health And Development

• Abe Jun

  Department Of Agricultural And Environmental Biology Graduate School Of Agricultural And Life Scienc

• TERAI Masaru

  Department of Pediatrics and Pediatric Intensive Care Medicine, Tokyo Women's Medical University Yachiyo Medical Center

• SAITO Hirohisa

  Department of Allergy and Immunology, National Research Institute for Child Health and Development

• HAMADA Hiromichi

  Department of Pediatrics and Pediatric Intensive Care Medicine, Tokyo Women's Medical University Yachiyo Medical Center

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