Vascular endothelial growth factor in acute Kawasaki disease

Abstract

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is an important regulator of angiogenesis and blood vessel permeability. Kawasaki disease (KD) is characterized by systemic vasculitis with increased vascular permeability, implying a possible role of VEGF in KD. To elucidate the involvement of VEGF in the pathogenesis of KD, we investigated 30 patients with acute KD, comparing the time course of plasma VEGF levels (n = 123) with clinical symptoms and laboratory findings. Compared with control values, the peak levels of plasma VEGF were significantly elevated (38 ± 26 vs 244 ± 248 pg/ml, p <0.001). The VEGF levels at the appearance of skin rash and/or edema of hands and feet were also elevated to 176 ± 163 pg/ml (p <0.001). In 7 patients (23%), the plasma VEGF levels remained increased after the resolution of the skin rash and peripheral edema. The VEGF levels were independent of gamma globulin therapy and levels of serum albumin and C-reactive protein. We also measured the plasma levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor α, both of which can upregulate VEGF in vitro. The plasma levels of VEGF were highly correlated with those of TGF-β1 (n = 63, r = 0.73, p <0.001) but not with those of tumor necrosis factor α. These findings suggest that the production of VEGF is increased and may be upregulated by TGF-β1 in acute KD. VEGF may be involved in the hyperpermeability of local blood vessels in acute KD.