Yasukawa Kumi, Terai Masaru, Shulman Stanford T, Toyozaki Tetsuya, Yajima Shigehiro, Kohno Yoichi, Rowley Anne H
Department of Pediatrics, Kawasaki Seitetsu Hospital, Chiba, Japan.
Circulation. 2002 Feb 12;105(6):766-9. doi: 10.1161/hc0602.103396.
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).
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 VEGF(165) 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).
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.
血管通透性增加是川崎病（KD）初始过程中的一个重要事件。血管内皮生长因子（VEGF）是诱导血管通透性增高的一个潜在相关候选因子。
我们研究了发病7天至5周的急性KD组织中VEGF及其受体（flt-1、KDR）的表达。还研究了增强VEGF(165)与KDR结合的神经纤毛蛋白-1。免疫组织化学证明，急性KD的许多器官（包括心脏和肺）中VEGF和flt-1表达丰富。VEGF和flt-1在所有出现水肿的血管中共定位。这些分子存在于内皮和血管中层，也存在于新生内膜中迁移的平滑肌细胞和浸润的巨噬细胞中。与对照组相比，急性KD的冠状动脉VEGF和flt-1上调，但KDR或神经纤毛蛋白-1未上调。KDR在发病7天时由血管表达，但在疾病后期不表达。与对照组相比，急性KD冠状动脉中的血浆蛋白与细胞外基质结合更广泛。此外，急性KD患者血清VEGF水平升高与低血清白蛋白相关（n = 220，r = -0.53，P < 0.001）。
这些发现表明，急性KD许多器官的血管中VEGF和flt-1上调。KDR的表达仅限于急性KD的早期阶段。VEGF在急性KD中的作用可能涉及促进血管通透性和巨噬细胞活化。低血清白蛋白可能表明急性KD中VEGF产生过多。
