Endothelial cell proteases: physiological role and regulation
Abstract
Endothelial cell-derived proteases can be classified according to their physiological role. The proteases involved in extracellular matrix degradation are important in endothelial cell migration and thereby in angiogenesis. They include the urokinase-type plasminogen activator (uPA) and the metalloproteases, collagenases, gelatinases and stromelysin. uPA secreted from endothelial cells remains associated with the cell membrane, on specific receptors localized in the vicinity of the receptors for plasminogen. This favours the local activation of plasminogen into plasmin. Plasmin, generated on the cell surface, is fully active as it is not inhibited by alpha 2-antiplasmin. Plasmin acts directly by degrading some components of the extracellular matrix and indirectly by activating the prometalloproteases. Secretion of PAI by migrating cells is generally stimulated by the same factors that induce uPA secretion, limiting the degradation of the matrix to the pericellular path. The degradation of the fibrin clot involves the tissue-type plasminogen activator tPA, which like the uPA activates plasminogen to plasmin. This system is also regulated by two different mechanisms. On the one hand, fibrin itself favours its own degradation by f...Continue Reading
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