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

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