Latent antithrombin and its detection, formation and turnover in the circulation
Latent antithrombin and its detection, formation and turnover in the circulation
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DOI：
10.1111/j.1538-7836.2004.01047.x
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发表时间：
2004-12-01
影响因子：
10.4
通讯作者：
Zhou, A
中科院分区：
文献类型：
--
作者：
Mushunje, A;Evans, G;Zhou, A
现在很明显，抗凝血酶（AT）的潜伏型和裂解型失活构象具有病理意义。使用单次电泳技术，可以定量评估2 μ l血浆中的这些构象，我们发现正常人循环中近3%的总AT处于潜在构象中。只观察到微量的裂解AT。在37℃的血浆中，AT活性的缓慢下降几乎完全是由于天然AT向其无活性潜伏形式的转变。在兔身上的初步研究也表明，潜伏形式，如cleaved，具有与天然AT相同的循环半衰期。我们推断，循环中潜伏AT的稳定浓度是由于每秒大约10（12）个AT分子的转变，由潜伏形式的等效清除来平衡。这项新技术的临床应用实例包括作为与AT缺乏相关的遗传变异的全面单步筛查，特别是它提供了监测导致休克综合征中AT丧失的变化的潜力。
It is now apparent that the inactivated latent and cleaved conformers of antithrombin (AT) are of pathological significance. Using a single-run electrophoretic technique that allows the quantitative assessment of these conformers in 2 muL plasma, we show that near 3% of the total AT in the circulations of normal individuals is in latent conformation. Only trace amounts of cleaved AT were observed. The slow decline in AT activity on incubation of plasma at 37degreesC was shown to be almost wholly due to a transition of native AT to its inactive latent form. Also initial studies in the rabbit indicate that the latent form, like the cleaved, has an identical circulatory half-life to that of native AT. We deduce that the steady concentration of latent AT in the circulation is due to the transition of some 10(12) molecules of AT per second balanced by an equivalent clearance of the latent form. Examples of clinical applications of the new technique include its use as a comprehensive single-step screen for genetic variants associated with AT deficiency, and notably the potential it provides to monitor the changes responsible for the loss of AT in the shock syndromes.