Assembly of plasmin-generating proteins on the surface of human endothelial cells.
Traditionally, plasmin generation has been conceptualized as a process oriented on the surface of a fibrin-containing thrombus. Recent work, however, indicated that plasminogen and its activators, tissue plasminogen activator (t-PA) and urokinase, can assemble on the surface of cultured human umbilical vein endothelial cells (HUVECs). On binding to HUVECs, plasminogen is activated by t-PA approximately 12-fold more efficiently than fluid-phase plasminogen, and is converted to a plasmin-modified form, possibly unique to cell surfaces. In addition, t-PA interacts with HUVECs at two sites. The major binding site preserves its activity and represents a true (relative molecular weight 40,000) membrane-associated exoreceptor. The low-density lipoprotein (LDL)-like lipoprotein, lipoprotein(a), is highly associated with atherosclerosis, bears striking sequence homology to plasminogen, and competes with plasminogen for cell surface binding. In summary, functional assembly of plasminogen and t-PA may represent an important thromboregulatory system.
Hajjar
K A
KA
Department of Medicine, Cornell University Medical College, New York, NY 10021.
D004730:Endothelium, Vascular / Q000378:metabolism*; D005341:Fibrinolysin / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017270:Lipoprotein(a); D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator