Highly accumulated platelet vascular endothelial growth factor in coagulant thrombotic region
Highly accumulated platelet vascular endothelial growth factor in coagulant thrombotic region
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DOI：
10.1046/j.1538-7836.2003.00475.x
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发表时间：
2003-12-01
影响因子：
10.4
通讯作者：
Maruyama, I
中科院分区：
文献类型：
--
作者：
Arisato, T;Hashiguchi, T;Maruyama, I
背景资料：血管内皮生长因子（VEGF）是一种内皮细胞特异性的有丝分裂原，可诱导血管生成和微血管通透性增高。最近，据报道巨核细胞和血小板在其细胞质中含有VEGF。目的：目的：阐明血小板中血管内皮生长因子（platelet VEGF）的生物活性及其作用，探讨其与血管血栓形成和动脉粥样硬化的关系。研究方法：采用免疫荧光和激光共聚焦显微镜分析骨髓涂片巨核细胞VEGF的定位。流式细胞术检测血小板内VEGF的表达。使用富血小板血浆和洗涤的血小板来分析凝血酶或明胶酶A（基质金属蛋白酶-2）刺激的血小板聚集期间VEGF的分泌。在血栓形成区域进行VEGF的免疫组织化学研究。结果和结论：巨核细胞和血小板是循环中VEGF的非常丰富的来源。明胶酶A与血管重塑密切相关，可增强血小板释放的VEGF水平。在血栓的纤维蛋白网中清楚地检测到VEGF。总之，血小板VEGF作为直接血管生成生长因子具有生物活性，并且可能与其他血小板细胞因子如血小板衍生生长因子、血小板衍生内皮细胞生长因子、转化生长因子（TGF）-α和TGF-β一起在伤口愈合和动脉粥样硬化中发挥非常重要的作用。
Background: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific potent mitogen that induces angiogenesis and microvascular hyperpermeability. Recently, it has been reported that megakaryocytes and platelets contain VEGF in their cytoplasm. Objectives: To elucidate and confirm the bioactivity and role of VEGF in platelets (platelet VEGF), which may be closely related to vascular thrombosis and atherosclerosis. Methods: The VEGF localization in megakaryocytes on bone marrow smears was analyzed by immunofluorescence and confocal laser scanning microscopic analysis. The intracellular VEGF expressed in platelets was determined by flow cytometric analysis. Platelet-rich plasma and washed platelets were used to analyze the secretion of VEGF during platelet aggregation by thrombin or gelatinase A (matrix metalloproteinase-2) stimulation. Immunohistochemical studies for VEGF in the thrombotic region were performed. Results and conclusions: Megakaryocytes and platelets are a very rich source of circulating VEGF. Gelatinase A, which is closely associated with vascular remodeling, enhances the VEGF levels released from platelets. VEGF was clearly detected in the fibrin nets of a thrombus. Taken together, platelet VEGF is bioactive as a direct angiogenic growth factor, and may play a very important role in wound healing and atherosclerosis in conjunction with other platelet cytokines such as platelet-derived growth factor, platelet-derived endothelial cell growth factor, transforming growth factor (TGF)-alpha, and TGF-beta.