Shen G X
Departments of Internal Medicine and Physiology, The University of Manitoba, Winnipeg, Manitoba, Canada.
Int J Mol Med. 1998 Feb;1(2):399-408.
Fibrinolysis is essential for maintaining the fluency of blood flow. Attenuated fibrinolytic activity has been frequently detected in coronary artery disease, peripheral vascular diseases, diabetes, hyperlipidaemia and obesity. The biologically active product of fibrinolytic system is plasmin. Generation of plasmin is regulated by plasminogen activators (PA) and their inhibitors (PAI). Vascular endothelial and smooth muscle cells synthesize tissue-type and urokinase-type PA (tPA and uPA) and their major physiological inhibitor, PAI-1. The production of fibrinolytic regulators is modulated by a number of biological factors related to thrombosis and atherosclerosis, including coagulation factors, hormones, growth factors, inflammatory mediators and lipoproteins. Several anticoagulants, including heparin, hirudin and hirulog-1, affect the production of fibrinolytic regulators in vascular cells. Studies in knockout mice demonstrated that mice deficient in PA or plasminogen are susceptible to thrombosis during inflammation or injury. Overexpression of uPA or deficiency of PAI-1 promotes neointima and aneurysm formation, which is probably due to active remodelling of extracellular matrix in vascular wall caused by excess plasmin. Long-term effect of treatment with thrombolytic agents or in atheroscleronic cardiovascular diseases remains to be defined. Future studies on determination of the role of PA and PAI in vascular remodelling may help understand the mechanism for neointima formation and orient the prevention of restenosis following vascular procedures.
纤维蛋白溶解对于维持血流顺畅至关重要。在冠状动脉疾病、外周血管疾病、糖尿病、高脂血症和肥胖症中，经常检测到纤维蛋白溶解活性减弱。纤维蛋白溶解系统的生物活性产物是纤溶酶。纤溶酶的生成受纤溶酶原激活剂（PA）及其抑制剂（PAI）的调节。血管内皮细胞和平滑肌细胞合成组织型和尿激酶型PA（tPA和uPA）及其主要生理抑制剂PAI-1。纤维蛋白溶解调节剂的产生受多种与血栓形成和动脉粥样硬化相关的生物因子调节，包括凝血因子、激素、生长因子、炎症介质和脂蛋白。几种抗凝剂，包括肝素、水蛭素和水蛭素-1，会影响血管细胞中纤维蛋白溶解调节剂的产生。对基因敲除小鼠的研究表明，缺乏PA或纤溶酶原的小鼠在炎症或损伤期间易患血栓形成。uPA的过度表达或PAI-1的缺乏会促进新生内膜和动脉瘤的形成，这可能是由于过量纤溶酶导致血管壁细胞外基质的活跃重塑所致。溶栓剂治疗或在动脉粥样硬化性心血管疾病中的长期效果仍有待确定。未来关于确定PA和PAI在血管重塑中作用的研究可能有助于理解新生内膜形成的机制，并为血管手术后再狭窄的预防提供指导。
