Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis.
Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis.
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DOI：
10.1111/j.1538-7836.2012.04797.x
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Montgomery RR
中科院分区：
文献类型：
--
作者：
Kanaji S;Fahs SA;Shi Q;Haberichter SL;Montgomery RR
血管性血友病因子(VWF)是一种在早期止血中起重要作用的糖蛋白。VWF在血管内皮细胞和巨核细胞/血小板中合成和储存。血浆VWF主要来源于内皮细胞，通常被认为是止血所必需的。巨核细胞合成的血管性血友病因子储存在血小板α颗粒中，活化后释放出来。储存在内皮细胞或巨核细胞/血小板中或存在于血浆中的VWF对止血的相对贡献尚不清楚。我们调查了内皮细胞来源的VWF是否在止血中起主要作用，而血小板来源的VWF的作用可以忽略不计，或者血小板来源的VWF是否也对止血有显著贡献。通过C57BL/6J(WT)和vWF基因敲除小鼠(vWF−/−)的对等骨髓移植，建立了仅在ECs(EC-vwf)或血小板(Plt-vwf)中表达vWF的小鼠。EC-VWF组血浆VWF水平与WT组相似。PLT-VWF小鼠的血浆中有微量的VWF，而血小板裂解物中的VWF水平与WT相当。EC-VWF尾部出血时间正常。有趣的是，PLT-VWF与VWF−/−相比，部分纠正了出血时间，并显著减少了失血量。与−/−相比，EC-VWF和PLT-VWF在剪切力作用下灌流到固定化胶原上的血小板的粘附性显著增加。在内皮细胞中合成的vwf足以支持vwf−/−小鼠的止血，在没有内皮细胞来源的vwf的情况下，巨核细胞/血小板产生的vwf也可以起到止血作用。
von Willebrand Factor (VWF) is a glycoprotein that plays an important role in primary hemostasis. VWF is synthesized and stored in endothelial cells (ECs) and megakaryocytes/platelets. Plasma VWF is primarily derived from ECs and is generally believed to be essential for hemostasis. VWF synthesized in megakaryocytes is stored in platelet α-granules from which it is released following platelet activation. The relative contribution of VWF stored in ECs or megakaryocytes/platelets, or present in plasma to hemostasis is not clear. We investigated whether EC-derived VWF plays the major role in hemostasis while the contribution of platelet-derived VWF is negligible, or if platelet-derived VWF also significantly contributes to hemostasis. Mice expressing VWF only in ECs (EC-VWF) or platelets (Plt-VWF) were created by reciprocal bone marrow transplantation between C57BL/6J (WT) and VWF knockout mice (VWF−/−). Plasma VWF levels in EC-VWF were similar to WT. Plt-VWF mice had a trace amount of VWF in their plasma while VWF levels in platelet lysate were comparable to WT. Tail bleeding time was normal in EC-VWF. Interestingly, Plt-VWF showed partially corrected bleeding time and significantly decreased blood loss volume compared to VWF−/−. Adhesion of platelets perfused over immobilized collagen under shear stress was significantly higher in both EC-VWF and Plt-VWF compared to VWF−/−. VWF synthesized in ECs is sufficient to support hemostasis in VWF−/− mice, and VWF produced in megakaryocytes/platelets can also contribute to hemostasis in the absence of EC-derived VWF.
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影响因子：
7.5
作者：
RODEGHIERO, F;CASTAMAN, G;TOSETTO, A
通讯作者：
TOSETTO, A
影响因子：
15.9
作者：
Shi, Qizhen;Wilcox, David A.;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.
影响因子：
20.3
作者：
Shi, Qizhen;Fahs, Scot A.;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.
DOI：
10.1161/atvbaha.108.168369
发表时间：
2008-09-01
影响因子：
8.7
作者：
De Meyer, Simon F.;Vandeputte, Nele;Vanhoorelbeke, Karen
通讯作者：
Vanhoorelbeke, Karen
影响因子：
20.3
作者：
Haberichter, Sandra L.;Balistreri, Michael;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.