Kooistra T, Schrauwen Y, Arts J, Emeis J J
Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
Int J Hematol. 1994 Jun;59(4):233-55.
The fibrinolytic activity of blood is to a large extent determined by the plasma level of tissue-type plasminogen activator (t-PA). Changes in the plasma level of t-PA are mainly achieved by the endothelium by two mechanisms: (a) a rapid, short-term release of t-PA, which occurs within minutes (acute release, regulated secretion) and (b) a long-term change in the rate of synthesis and constitutive secretion of t-PA. The rapid t-PA release response of the endothelium upon stimulation may play an important role in the dissolution of fibrin at the initial event of fibrin formation, and hence in the prevention of thrombus formation. The rate of constitutive t-PA secretion is an important determinant of the actual levels of t-PA under basal and stimulated conditions. Our insight into the regulation of the synthesis and release of t-PA has extended markedly in the last decade and still adapts by the continuous stream of new experimental data. In this review we summarize our present knowledge about the factors, including intracellular signalling pathways, promoter elements and transcription factors involved in the modulation of t-PA gene expression, with particular reference to the regulation in human endothelial cells. We also discuss the mechanisms underlying acute release of t-PA from the endothelium, and provide evidence that the regulated and constitutive secretion of t-PA are interrelated in several aspects.
血液的纤溶活性在很大程度上由组织型纤溶酶原激活物（t-PA）的血浆水平决定。t-PA血浆水平的变化主要由内皮细胞通过两种机制实现：（a）t-PA的快速、短期释放，在数分钟内发生（急性释放，调节性分泌）；（b）t-PA合成和组成性分泌速率的长期变化。内皮细胞在受到刺激时快速释放t-PA的反应可能在纤维蛋白形成的初始事件中纤维蛋白溶解过程中起重要作用，从而在预防血栓形成中发挥作用。组成性t-PA分泌速率是基础和刺激条件下t-PA实际水平的重要决定因素。在过去十年中，我们对t-PA合成和释放调节的认识有了显著扩展，并且仍在随着源源不断的新实验数据而不断调整。在这篇综述中，我们总结了目前关于调节t-PA基因表达的因素的知识，包括细胞内信号通路、启动子元件和转录因子，特别提及了人类内皮细胞中的调节情况。我们还讨论了内皮细胞急性释放t-PA的潜在机制，并提供证据表明t-PA的调节性分泌和组成性分泌在多个方面相互关联。
