Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage
Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage
复制标题
DOI：
10.1073/pnas.0510412103
复制
发表时间：
2006-01-24
影响因子：
11.1
通讯作者：
Wagner, DD
中科院分区：
文献类型：
--
作者：
Kisucka, J;Butterfield, CE;Wagner, DD
血小板含有促血管生成因子和抗血管生成因子，但人们对它们在血管生成中的调节作用知之甚少。尽管之前的研究表明血小板在体外刺激血管生成，但血小板在体内血管生成中的作用很大程度上是未知的。为了解决这个问题，我们在四种动物模型中使用了两种体内方法，即角膜微袋测定和基质胶模型：血小板减少症、Lyst(bg)（血小板储存池缺陷）、糖蛋白（GP）Ib α/IL4R转基因（缺乏细胞外GPIb α、冯维勒布兰德因子受体以及其他粘附和促凝血蛋白）和Fc gamma R-/-（缺乏功能性） GPVI，胶原蛋白受体）小鼠。通过腹腔注射使成年小鼠血小板减少。施用抗血小板抗体。在角膜测定中，血小板减少症小鼠的生长血管数量较低，并且与对照 IgG 治疗的小鼠相比，它们显示出出血现象显着增加。血小板减少症小鼠在基质胶模型中还表现出更多的蛋白质渗漏并出现血肿。 GPIlb α/IL4R转基因小鼠在两种测定中均表现出出血增加，但其严重程度低于血小板耗尽的小鼠。 Fc gamma R-/- 和 LyStbg 小鼠在实验性血管生成中未显示缺陷。活体显微镜显示，与成熟静止皮肤血管相比，血小板对 Matrigel 血管生成血管的粘附增加了 3 倍以上。我们的结果表明，血小板的存在不仅刺激血管生成血管生长，而且在防止血管生成血管出血方面发挥着关键作用。由 GPIba 介导的血小板粘附功能对该过程有显着贡献。
Platelets contain both pro- and antiangiogenic factors, but their regulatory role in angiogenesis is poorly understood. Although previous studies showed that platelets stimulate angiogenesis in vitro, the role of platelets in angiogenesis in vivo is largely uncharacterized. To address this topic, we used two in vivo approaches, the cornea micropocket assay and the Matrigel model, in four animal models: thrombocytopenic, Lyst(bg) (platelet storage pool deficiency), glycoprotein (GP) Ib alpha/IL4R transgenic (lacking extracellular GPIb alpha, the receptor for von Willebrand factor as well as other adhesive and procoagulant proteins), and Fc gamma R-/- (lacking functional GPVI, the collagen receptor) mice. Adult mice were rendered thrombocytopenic by i.p. administration of an antiplatelet antibody. The number of growing vessels in the thrombocytopenic mice was lower in the cornea assay, and they showed significantly increased appearance of hemorrhage compared with mice treated with control IgG. The thrombocytopenic mice also showed more protein leakage and developed hematomas in the Matrigel model. GPIlb alpha/IL4R transgenic mice presented increased hemorrhage in both assays, but it was less severe than in the platelet-depleted mice. Fc gamma R-/- and LyStbg mice showed no defect in experimental angiogenesis. Intravital microscopy revealed a > 3-fold increase in platelet adhesion to angiogenic vessels of Matrigel compared with mature quiescent skin vessels. Our results suggest that the presence of platelets not only stimulates angiogenic vessel growth but also plays a critical role in preventing hemorrhage from the angiogenic vessels. The adhesion function of platelets, as mediated by GPIba, significantly contributes to the process.