Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor.

摘要: Endothelial cells impart thromboresistance to the blood vessel wall. As modulators of fibrinolytic activity, these synthesize and secrete tissue plasminogen activator (t-PA) as well its physiologic inhibitor, inhibitor-1. In addition, endothelial support membrane-associated assembly activator. Recently, an M(r) approximately 40,000 protein expressed on has been shown interact noncompetitively through disparate mechanisms with both t-PA plasminogen, suggesting trimolecular enzyme, substrate, receptor (Hajjar, K. A. 1991. J. Biol. Chem. 266:21962-21970). present study, treatment cultured DL-homocysteine was specifically associated a selective reduction in cellular binding sites for t-PA. This 65% decrease 60% cell-associated activity. No change affinity or maximal number observed. Matrix-associated were not affected. These data suggest new mechanism whereby homocysteine may perturb cell function, thus promoting prothrombotic state at surface