Fibrin-bound lipoprotein(a) promotes plasminogen binding but inhibits fibrin degradation by plasmin.
Conflicting results have been obtained from studies of the effects of lipoprotein(a) [Lp(a)] on plasminogen binding to fibrin and fibrin-dependent activation by tissue plasminogen activation (t-PA). We performed binding studies of Glu-plasminogen (0-16 microM) to immobilized D-dimer +/- Lp(a) (0.20 microM). In the absence of Lp(a), Scatchard analysis revealed a binding constant of KD = 1.01 +/- 0.18 microM, with two plasminogen binding sites per D-dimer. In the presence of Lp(a), a lower affinity (KD 3.10 +/- 0.23 microM) was found, but five binding sites were present, suggesting that plasminogen bound to fibrin-bound Lp(a) rather than to D-dimer. Consistent with this explanation was the finding that when D-dimer-coated plates were first precoated with Lp(a) before plasminogen was added, similar lower affinity plasminogen binding was found. This binding to Lp(a) was fibrin-dependent since, in its absence, plasminogen failed to bind to Lp(a). Therefore, a conformational change in Lp(a) appeared to be required for plasminogen binding to occur. This finding of two types of binding sites of different affinities helps to explain why Lp(a) has been reported to inhibit plasminogen binding to fibrin in studies in which only low concentrations of plasminogen (< 0.4 microM) were used. At these concentrations, few of the low-affinity binding sites on fibrin-bound Lp(a) will be occupied by plasminogen, an effect that was found to be exaggerated by the omission of NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)
Liu
J
J
Vascular Research Laboratory, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Harpel
P C
PC
Gurewich
V
V
D000595:Amino Acid Sequence; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000378:metabolism*; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D017270:Lipoprotein(a); D005337:Fibrin; D010958:Plasminogen; D005341:Fibrinolysin