Pepper M S, Montesano R, Mandriota S J, Orci L, Vassalli J D
Department of Morphology, University of Geneva Medical Center, Switzerland.
Enzyme Protein. 1996;49(1-3):138-62. doi: 10.1159/000468622.
Extracellular proteolysis is required for matrix degradation and the regulation of cytokine activity during angiogenesis, and this is dependent on a cohort of proteases and protease inhibitors produced by endothelial and nonendothelial cells. The plasminogen activator (PA)/plasmin system has been extensively investigated in these processes, and descriptive studies have demonstrated that urokinase-type PA (uPA), uPA receptor (uPAR) and PA inhibitor-1 (PAI-1) are expressed by endothelial cells during angiogenesis in vivo. In vitro studies have led to the notion that normal capillary morphogenesis is dependent on a protease-antiprotease equilibrium. These findings are discussed in the context of recent observations on uPA-, uPAR-, PAI-1 and plaminogen-deficient mice, in which developmental and physiological angiogenesis appear to occur normally. This has led to a reevaluation of the role of the PA/plasmin system during angiogenesis. In particular, these observations raise the possibility that the role of this system may be limited to situations in which endothelial cells encounter and must degrade fibrin in order to form new capillary sprouts.
细胞外蛋白水解作用对于血管生成过程中的基质降解和细胞因子活性调节是必需的，这依赖于内皮细胞和非内皮细胞产生的一系列蛋白酶和蛋白酶抑制剂。纤溶酶原激活剂（PA）/纤溶酶系统在这些过程中已得到广泛研究，描述性研究表明，在体内血管生成过程中，内皮细胞表达尿激酶型PA（uPA）、uPA受体（uPAR）和PA抑制剂-1（PAI-1）。体外研究得出这样的观点，即正常的毛细血管形态发生依赖于蛋白酶-抗蛋白酶平衡。结合最近对uPA、uPAR、PAI-1和纤溶酶原缺陷小鼠的观察结果对这些发现进行了讨论，在这些小鼠中，发育性和生理性血管生成似乎正常发生。这导致对PA/纤溶酶系统在血管生成过程中的作用进行重新评估。特别是，这些观察结果增加了这样一种可能性，即该系统的作用可能仅限于内皮细胞遇到并必须降解纤维蛋白以形成新的毛细血管芽的情况。
