Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis
Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis
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DOI：
10.4049/jimmunol.164.11.5922
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发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Adachi, M
中科院分区：
文献类型：
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作者：
Lu, J;Kasama, T;Adachi, M
我们研究了血管生成因子、血管内皮生长因子 (VEGF) 在 II 型胶原诱导性关节炎 (CIA) 进化过程中的表达和功能。生物活性 VEGF 的表达时间过程与两种特定 VEGF 受体 Flk-1 和 Flt-1 的表达以及关节疾病的进展平行。此外，VEGF 表达水平与新血管形成程度（由 vWF 水平定义）和关节炎严重程度相关。巨噬细胞和成纤维细胞样细胞浸润发炎部位，然后被其他炎症介质激活，可能是 VEGF 的重要来源，因此可能在 CIA 的发展过程中调节血管生成。在关节炎发病前给CLA小鼠施用抗VEGF抗血清可以延缓发病，减轻关节炎的严重程度，并减少关节炎关节的VWF含量。相比之下，在疾病发病后施用抗VEGF抗血清对关节炎的进展或最终严重程度没有影响。这些数据表明 VEGF 在关节炎发展的早期阶段发挥着至关重要的作用，影响新血管形成和实验诱导的滑膜炎的进展。
We have examined the expression and function of the angiogenic factor, vascular endothelial growth factor (VEGF) during the evolution of type II collagen-induced arthritis (CIA), Biologically active VEGF was expressed along a time course that paralleled the expression of two specific VEGF receptors, Flk-1 and Flt-1, and the progression of joint disease. Moreover, Levels of VEGF expression correlated with the degree of neovascularization, as defined by vWF levels, and arthritis severity. Macrophage- and fibroblast-like cells, which infiltrated inflamed sites and were then activated by other inflammatory mediators, are probably important sources of VEGF and may thus regulate angiogenesis during the development of CIA. Administration of anti-VEGF antiserum to CLA mice before the onset of arthritis delayed the onset, reduced the severity, and diminished the VWF content of arthritic joints, By contrast, administration of anti-VEGF antiserum after the onset of the disease had no effect on the progression or ultimate severity of the arthritis. These data suggest that VEGF plays a crucial role during an early stage of arthritis development, affecting both neovascularization and the progression of experimentally induced synovitis.