Differential role of platelet granular mediators in angiogenesis
Differential role of platelet granular mediators in angiogenesis
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DOI：
10.1016/j.cardiores.2004.04.012
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发表时间：
2004-08-01
影响因子：
10.8
通讯作者：
Varon, D
中科院分区：
文献类型：
--
作者：
Brill, A;Elinav, H;Varon, D
目的：血小板含有多种调节血管生成反应的物质。然而，血小板在血管发育中的调节作用仍有待阐明。我们研究了血小板作为一种细胞系统对血管生成的综合作用。研究方法：应用以下方法：（a）体外-主动脉环测定和趋化性测定;（B）体内-将含有血小板的基质胶塞皮下注射到小鼠中，然后进行血管生成反应的免疫组织化学分析。结果如下：在体外大鼠主动脉环模型中，血小板通过VEGF和bFGF刺激血管形成，而血小板因子-4的阻断促进了这种作用。将血小板添加到基质胶中，然后将其皮下注射到小鼠中，导致成纤维细胞密集迁移到基质胶中以及新生毛细血管的形成。这种血小板效应通过bFGF、VEGF和乙酰肝素酶介导。此外，血小板释放被发现诱导内皮细胞趋化性。这种作用是由血小板内bFGF、PDGF、VEGF和乙酰肝素酶的协同作用介导的。结论：血小板影响血管生成反应的不同阶段，尽管存在血管生成抑制剂（如血小板因子4），但有促血管生成净效应的趋势。虽然bFGF和VEGF的伴随作用似乎对血管形成的整个过程（主动脉环和基质胶模型）是必不可少的，但PDGF和乙酰肝素酶仅在迁移阶段有效。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objectives: Platelets contain numerous substances regulating angiogenic response. However, the regulatory role of platelets in blood vessel development remains to be elucidated. We investigated the comprehensive effect of platelets as a cellular system on angiogenesis. Methods: The following approaches were applied: (a) in vitro-aortic ring assay and chemotaxis assay; (b) in vivo-injection of platelet-containing matrigel plug subcutaneously into a mouse followed by immunohistochemical analysis of angiogenic response. Results: Platelets stimulated formation of blood vessels in vitro in the rat aortic ring model via VEGF and bFGF, while blocking of platelet factor-4 promoted this effect. Addition of platelets to the matrigel followed by its subcutaneous injection into a mouse resulted in an intensive migration of fibroblasts into the matrigel as well as formation of blood capillaries de novo. This platelet effect was mediated through bFGF, VEGF, and heparanase. Furthermore, platelet releasate was found to induce endothelial cell chemotaxis. This effect was mediated by a concerted action of intraplatelet bFGF, PDGF, VEGF, and heparanase. Conclusion: Platelets affect different stages of the angiogenic response with a trend to a pro-angiogenic net effect despite the presence of angiogenesis inhibitors such as platelet factor 4. While a concomitant effect of bFGF and VEGF seemed to be essential for the entire process of vessel formation (aortic ring and matrigel models), PDGF and heparanase were effective only at the migration stage. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.