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(Circulation. 2002;105:766.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Systemic Production of Vascular Endothelial Growth Factor and fms-Like Tyrosine Kinase-1 Receptor in Acute Kawasaki Disease

Kumi Yasukawa, MD; Masaru Terai, MD; Stanford T. Shulman, MD; Tetsuya Toyozaki, MD; Shigehiro Yajima, MD; Yoichi Kohno, MD; Anne H. Rowley, MD

From the Departments of Pediatrics, Kawasaki Seitetsu Hospital (K.Y.), Chiba, Japan, and Takayama Red Cross Hospital (S.Y.), Gifu, Japan; Department of Pediatrics (K.Y., M.T., Y.K.) and Institute of Pulmonary Cancer Research (T.T.), Chiba University School of Medicine, Chiba, Japan; and Departments of Pediatrics (S.T.S., A.H.R.) and Microbiology and Immunology (A.H.R.), Northwestern University Medical School, Chicago, Ill.

Correspondence to Masaru Terai, MD, Department of Pediatrics, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan. E-mail terai{at}med.m.chiba-u.ac.jp

Background— Increased vascular permeability is an important event during the initial process of Kawasaki disease (KD). One potential responsible candidate for the induction of vascular hyperpermeability is vascular endothelial growth factor (VEGF).

Methods and Results— We investigated the expression of VEGF and its receptors (flt-1, KDR) in acute KD tissues at 7 days to 5 weeks of illness. Neuropilin-1, which enhances the binding of VEGF₁₆₅ to KDR, was also studied. Abundant expression of VEGF and flt-1 was documented immunohistochemically in many organs from acute KD, including heart and lung. VEGF and flt-1 were colocalized in all vessels that showed edema. These molecules resided in endothelium and vascular media and also in migrating smooth muscle cells in neointima and infiltrating macrophages. Compared with controls, coronary vessels of acute KD had upregulation of VEGF and flt-1 but not KDR or neuropilin-1. KDR was expressed by vessels at 7 days of illness but not later in the illness. Plasma proteins were more extensively bound to the extracellular matrix in coronary vessels in acute KD than controls. Furthermore, elevation of serum VEGF levels was correlated with low serum albumin in acute KD (n=220, r=-0.53, P<0.001).

Conclusions— These findings suggest that VEGF and flt-1 are upregulated in blood vessels in many organs of acute KD. Expression of KDR was limited to the early stage of acute KD. The roles of VEGF in acute KD may involve promotion of vascular permeability and macrophage activation. Low serum albumin may indicate overproduction of VEGF in acute KD.

Key Words: Kawasaki disease • growth substances • receptors

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