Plasmin catalyzes binding of lipoprotein (a) to immobilized fibrinogen and fibrin.
Lipoprotein (a) [Lp(a)] is a plasma component whose concentration is related to the development of atherosclerosis, although the underlying mechanisms are not known. Lp(a) contains a unique structure, apolipoprotein (a), that shares partial homology with plasminogen. We now report that plasmin catalyzes the binding of Lp(a) to both immobilized fibrinogen and fibrin in a manner analogous to our previously reported studies with plasminogen. Plasmin treatment of immobilized fibrinogen induces a 3.7-fold increase in Lp(a) binding. Low density lipoprotein, molecules similar to Lp(a) but lacking apolipoprotein (a), bind poorly to immobilized fibrinogen and binding is not increased by plasmin. Trypsin but not neutrophil elastase also increases the binding of Lp(a) to fibrinogen. Lp(a) also complexes to plasmin-fibrinogen digests, and binding increases in proportion to the time of plasmin-induced fibrinogen degradation. Lp(a) binding is lysine-binding site dependent as it is inhibited by epsilon-aminocaproic acid. Lp(a) inhibits the binding of plasminogen to plasmin-modified immobilized fibrinogen, indicating that both molecules compete for similar lysine-binding sites. These findings demonstrate an affinity between Lp(a) and protease-modified fibrinogen or fibrin and thereby provide a potential mechanism to explain the association between thrombosis, coronary atherosclerosis, and increased blood concentrations of Lp(a).
Harpel
P C
PC
Department of Medicine, New York Hospital-Cornell Medical Center, NY 10021.
Gordon
B R
BR
Parker
T S
TS
D001161:Arteriosclerosis / Q000097:blood; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005341:Fibrinolysin / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008239:Lysine; D010196:Pancreatic Elastase / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000494:pharmacology
D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D005337:Fibrin; D005340:Fibrinogen; D010196:Pancreatic Elastase; D014357:Trypsin; D005341:Fibrinolysin; D008239:Lysine