© 2000 American Heart Association, Inc.
Thrombosis |
Effect of Individual Plasma Lipoprotein(a) Variations In Vivo on Its Competition With Plasminogen for Fibrin and Cell Binding
An In Vitro Study Using Plasma From Children With Idiopathic Nephrotic Syndrome
From INSERM U.143, Hôpital de Bicêtre (T.S., S.L., E.A.-C.), Bicêtre, France, and the Departments of Pediatric Nephrology (V.B., C.L.) and Hematology (L.M., M.-F.H.-R., N.S.), Hôpital Robert-Débré, Paris, France.
Correspondence to Dr E. Anglés-Cano, INSERM U.143, Hémostase-Biologie Vasculaire, 84 rue du Général Leclerc, F-94276-Cedex, Bicêtre, France. E-mail angles{at}infobiogen.fr
Abstract—Simultaneous natural changes in lipoprotein(a) [Lp(a)] and plasminogen occur in the nephrotic syndrome and offer a unique opportunity to investigate their effects on plasminogen activation under conditions fashioned in vivo. Plasminogen, Lp(a), and apolipoprotein(a) in plasma were characterized, and their competitive binding to carboxy-terminal lysine residues of fibrin and cell membrane proteins was determined in nephrotic children during a flare-up of the disease (61 cases) and after 6 weeks (33 cases) and 6 months (42 cases) of remission. Low plasminogen concentrations (median 1.34 µmol/L, range 0.39 to 1.96 µmol/L) and high Lp(a) levels (median 0.27 g/L, range 0.07 to 2.57 g/L) were detected at flare-up. These changes were associated with an increased Lp(a) binding ratio onto fibrin (3.13±0.48) and cells (1.53±0.24) compared with binding ratios of control children (1.31±0.19 and 1.05±0.07, respectively) with normal plasminogen and low Lp(a) (median 0.071 g/L). After 6 weeks and 6 months of remission, the values for net decrease in Lp(a) binding to fibrin were 1.7±0.22 (after 6 weeks) and 1.88±0.38 (after 6 months) and were correlated with low Lp(a) concentrations (median 0.2 g/L, range 0.07 to 0.8 g/L; and median 0.12 g/L, range 0.07 to 1.34 g/L) and inversely associated with increased plasminogen levels (median 1.82 µmol/L, range 1.4 to 2.1 µmol/L; and median 1.58 µmol/L, range 1.1 to 2.1 µmol/L). These studies provide the first quantitative evidence that binding of Lp(a) to lysine residues of fibrin and cell surfaces is directly related to circulating levels of both plasminogen and Lp(a) and that these glycoproteins may interact as competitive ligands for these biological surfaces in vivo. This mechanism may be of relevance to the atherothrombotic role of Lp(a), particularly in nephrotic patients.
Key Words: lipoprotein(a) • apolipoprotein(a) isoforms • binding, competitive • plasminogen inhibition • lysine binding site
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