Evidence for factor IX-independent roles for factor XIa in blood coagulation.
Evidence for factor IX-independent roles for factor XIa in blood coagulation.
复制标题
因子IX因子在血液凝结中的不依赖性作用的证据。
DOI：
10.1111/jth.12435
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Gailani D
中科院分区：
文献类型：
--
作者：
Matafonov A;Cheng Q;Geng Y;Verhamme IM;Umunakwe O;Tucker EI;Sun MF;Serebrov V;Gruber A;Gailani D
因子（f）XIa传统上被指定在凝血期间fIX活化中起作用。然而，最近的证据表明，这种蛋白酶可能有额外的血浆底物。确定在不存在fIX的情况下fXIa是否促进血浆中凝血酶生成和凝血，并确定fXI缺乏是否在小鼠中产生不依赖于fIX的抗血栓形成作用。检测了FXIa、fXIa变体和抗fXIa抗体在不存在fIX的情况下对血浆凝血和凝血酶生成的影响，以及对纯化凝血因子活化的影响。在动脉血栓形成模型中，将具有fIX和fXI组合缺陷的小鼠与缺乏fIX或fXI的小鼠进行比较。在fIX缺陷血浆中，fXIa诱导凝血酶产生，抗fXIa抗体延长凝血时间。该过程涉及fXIa介导的fX和fV向其活性形式的转化。通过fXIa激活fV需要fXIa重链上的A3结构域，而fX的激活不需要。与fIX激活不同，fXIa激活FX不是钙依赖性过程。缺乏fIX和fXI的小鼠比fXI缺陷或fIX缺陷的小鼠对氯化铁诱导的颈动脉闭塞更具抵抗力。除了其作为fIX的激活剂的主要作用之外，fXIa还可以通过激活fX和fV来促进凝血。由于后一种反应不需要钙，它们可能对接触激活触发的体外凝血试验做出重要贡献。这些反应可能与fXIa在止血和促进血栓形成中的作用有关。
Factor (f) XIa is traditionally assigned a role in fIX activation during coagulation. However, recent evidence suggests this protease may have additional plasma substrates. To determine if fXIa promotes thrombin generation and coagulation in plasma in the absence of fIX, and to determine if fXI deficiency produces an antithrombotic effect in mice independent of fIX. FXIa, fXIa variants, and anti-fXIa antibodies were tested for their effects on plasma coagulation and thrombin generation in the absence of fIX, and for their effects on activation of purified coagulation factors. Mice with combined fIX and fXI deficiency were compared to mice lacking either fIX or fXI in an arterial thrombosis model. In fIX-deficient plasma, fXIa induced thrombin generation and anti-fXIa antibodies prolonged clotting times. This process involved fXIa-mediated conversion of fX and fV to their active forms. Activation of fV by fXIa required the A3 domain on the fXIa heavy chain, while activation of fX did not. FX activation by fXIa, unlike fIX activation, was not a calcium-dependent process. Mice lacking both fIX and fXI were more resistance to ferric chloride-induced carotid artery occlusion than fXI-deficient or fIX-deficient mice. In addition to its predominant role as an activator of fIX, fXIa may contribute to coagulation by activating fX and fV. As the latter reactions do not require calcium, they may make important contributions to in vitro clotting assays triggered by contact activation. The reactions may be relevant to fXIa's roles in hemostasis and in promoting thrombosis.
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影响因子：
3.2
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1004741107
发表时间：
2010-05-18
影响因子：
11.1
作者：
Maas, Coen;Meijers, Joost C. M.;Urbanus, Rolf T.
通讯作者：
Urbanus, Rolf T.