Swedenborg J
Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
Blood Coagul Fibrinolysis. 1998 Nov;9 Suppl 3:S7-10.
Antithrombin (AT) is the most important physiological inhibitor of thrombin. This effect can be increased more than a 1000-fold by heparin and heparin-like glycosaminoglycans, which induce a conformational change in the molecule. Two isoforms of AT exist in plasma: alpha and beta. The beta-isoform lacks one of four carbohydrate side-chains that are present on the alpha-isoform. The beta-isoform, which constitutes approximately 10% of plasma AT, has a higher affinity for heparin and heparin-like glycosaminoglycans than the alpha-isoform. In contrast to their distribution in plasma, the two isoforms of AT appear to be present in the same proportions in the vessel wall. After balloon injury of rabbit aorta, thrombin can be detected in the vessel wall, an effect that is inhibited by treatment with AT. The inhibitory effect of AT on thrombin coagulant activity in the injured vessel wall is attributable to the beta-isoform. The appearance of thrombin in the injured vessel wall can also be inhibited by heparin treatment, but this requires heparin to be circulating in plasma at the time of excision of the injured vessel wall. Thrombin has been suggested as a mitogen for smooth muscle cells. This effect of thrombin can be inhibited by AT, an inhibition that is increased by heparin in a concentration-dependent manner. The alpha-isoform of AT has a lower inhibitory capacity for the thrombin-induced proliferation of smooth muscle cells in the absence of heparin, compared with the beta-isoform, which is an effective inhibitor alone. This indicates that the beta-isoform of AT may use glycosaminoglycans produced by smooth muscle cells as a cofactor. In conclusion, the beta-isoform of AT appears to be an effective inhibitor of the thrombin coagulant activity induced by vessel wall injury. It is also a more effective inhibitor of the thrombin-induced proliferation of smooth muscle cells than the alpha-isoform.
抗凝血酶（AT）是凝血酶最重要的生理性抑制剂。肝素和类肝素糖胺聚糖可使这种抑制作用增强1000倍以上，它们能诱导该分子发生构象变化。血浆中存在两种抗凝血酶同工型：α型和β型。β型同工型缺少α型同工型所具有的四个碳水化合物侧链中的一个。β型同工型约占血浆AT的10%，它对肝素和类肝素糖胺聚糖的亲和力高于α型同工型。与它们在血浆中的分布情况不同，抗凝血酶的这两种同工型在血管壁中的比例似乎相同。兔主动脉球囊损伤后，可在血管壁中检测到凝血酶，而抗凝血酶治疗可抑制这种现象。抗凝血酶对损伤血管壁中凝血酶凝血活性的抑制作用归因于β型同工型。肝素治疗也可抑制损伤血管壁中凝血酶的出现，但这要求在切除损伤血管壁时肝素在血浆中循环。凝血酶被认为是平滑肌细胞的促有丝分裂原。抗凝血酶可抑制凝血酶的这种作用，肝素可使其抑制作用呈浓度依赖性增强。在没有肝素的情况下，与单独作为有效抑制剂的β型同工型相比，抗凝血酶α型同工型对凝血酶诱导的平滑肌细胞增殖的抑制能力较低。这表明抗凝血酶β型同工型可能将平滑肌细胞产生的糖胺聚糖用作辅因子。总之，抗凝血酶β型同工型似乎是血管壁损伤诱导的凝血酶凝血活性的有效抑制剂。它也是比α型同工型更有效的凝血酶诱导的平滑肌细胞增殖抑制剂。
