Inhibition of Thrombin by Antithrombin III and Heparin Cofactor II In Vivo
Inhibition of Thrombin by Antithrombin III and Heparin Cofactor II In Vivo
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体内抗凝血酶 III 和肝素辅因子 II 对凝血酶的抑制
作者：
Long;L. Dewar;Yingqi Song;M. Kulczycky;Blajchman Morris;J. Fenton;M. Andrew;M. Delorme;J. Ginsberg;K. Preissner;F. Ofosu
凝血酶在静脉和动脉血栓形成的发病机制中的关键作用以及糖胺聚糖作为抗血栓药物的有效性是众所周知的。抗凝血酶III是凝血酶的主要抑制剂，肝素增强其抑制作用是肝素临床应用的基础。最近的临床和实验研究表明，另一种糖胺聚糖硫酸皮肤素是一种有效的抗血栓药物。硫酸皮肤素催化肝素辅因子II对凝血酶的抑制作用。肝素辅因子II的浓度是较高的血浆中的个人先天性抗凝血酶III缺乏症和孕妇比对照组。肝素辅因子II作为生理性凝血酶抑制剂的作用尚不清楚。酶联免疫吸附试验被用来量化凝血酶-肝素辅因子II和凝血酶-抗凝血酶III内源性的成人抗凝血酶III-汉密尔顿缺陷的受试者，他们的兄弟姐妹与正常的抗凝血酶III水平，孕妇在足月和分娩后3至5天的血浆。凝血酶-抗凝血酶III和凝血酶-肝素辅因子II与玻连蛋白复合在所有血浆中检测到。值得注意的是，凝血酶-肝素辅因子II-玻连蛋白的浓度在先天性抗凝血酶III缺陷受试者的血浆中以及在分娩前和分娩后的血浆中均高于正常受试者。此外，凝血酶-肝素辅因子II的浓度在分娩后3至5天降低，反映了胎盘产生的催化活性硫酸皮肤素的消失。因此，肝素辅因子II通常在体内使凝血酶失活，其作用在与高水平肝素辅因子II和/或硫酸皮肤素相关的病症中增加。
Summary The critical role of thrombin in the pathogenesis of venous and arterial thrombosis, and the effectiveness of glycosaminoglycans as antithrombotic drugs are well known. Antithrombin III is a major inhibitor of thrombin and augmentation of its inhibitory actions by heparin is the basis for the clinical uses of heparin. Recent clinical and experimental studies have demonstrated that another glycosaminoglycan, dermatan sulfate, is an effective antithrombotic drug. Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital antithrombin III deficiency and pregnant women than controls. The role of heparin cofactor II as a physiologic thrombin inhibitor is unknown. Enzyme-linked immunosorbent assays were used to quantify thrombin-heparin cofactor II and thrombin-antithrombin III endogenous to the plasmas of adult antithrombin III-Hamilton deficient subjects, their siblings with normal antithrombin III levels, pregnant women at term and 3 to 5 days after delivery. Both thrombin-antithrombin III and thrombin-heparin cofactor II complexed with vitronectin were detected in all the plasmas. Significantly, the concentrations of thrombin-heparin cofactor II-vitronectin were higher in the plasmas of congenital antithrombin III deficient subjects and in pre- and post-delivery plasmas than those of normal subjects. In addition, the concentrations of thrombin-heparin cofactor II decreased 3 to 5 days after delivery, reflecting the disappearance of the catalytically active dermatan sulfate elaborated by the placenta. Thus, heparin cofactor II normally inactivates thrombin in vivo, with its role increasing in conditions associated with high levels of heparin cofactor II and/or dermatan sulfate.
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抗凝血酶 III 和抗凝血酶 III 复合物的体内代谢。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shifman,MA;Pizzo,SV
通讯作者：
Pizzo,SV
抗凝血酶：结构和功能。
影响因子：
3.6
作者：
Pratt,CW;Church,FC
通讯作者：
Church,FC
妊娠和口服避孕药使用期间血浆中肝素辅因子 II 的活性。
DOI：
--
发表时间：
1989
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
Massouh,M;Jatoi,A;Gordon,EM;Ratnoff,OD
通讯作者：
Ratnoff,OD
先天性抗凝血酶缺乏症无症状患者血液中 Xa 因子活性升高。
DOI：
10.1172/jci112040
发表时间：
1985
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Bauer,KA;Goodman,TL;Kass,BL;Rosenberg,RD
通讯作者：
Rosenberg,RD
影响因子：
3.3
作者：
R. Rosenberg;K. Bauer
通讯作者：
R. Rosenberg;K. Bauer