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

Simultaneous natural changes in lipoprotein(a) [Lp(a)] and plasminogen occu r in the nephrotic syndrome and offer a unique opportunity to investigate t heir effects on plasminogen activation under conditions fashioned in vivo. Plasminogen, Lp(a), and apolipoprotein(a) in plasma were characterized, and their competitive binding to carboxyterminal 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 mu mol/L, range 0.39 to 1.96 mu mol/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) (medi an 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 1.8 8+/-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 (medi an 1.82 mu mol/L, range 1.4 to 2.1 mu mol/L; and median 1.58 mu mol/L, rang e 1.1 to 2.1 mu mol/L). These studies provide the first quantitative eviden ce 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 th at these glycoproteins may interact as competitive ligands for these biolog ical surfaces in vivo. This mechanism may be of relevance to the atherothro mbotic role of Lp(a), particularly in nephrotic patients.