The antifibrinolytic effect of lipoprotein(a) in heterozygous subjects is modulated by the relative concentration of each of the apolipoprotein(a) isoforms and their affinity for fibrin.
Individuals heterozygous for the apolipoprotein(a) [apo(a)] trait have phenotypes combining two different lipoprotein(a) [La(a)] particle suspecies that are present in plasma at a different concentration. Evaluation of the ability of each of these isoforms to bind to fibrin and affect plasminogen binding is essential to assess the pathogenic role of Lp(a) in these subjects; therefore, fractions containing different ratios of Lp(a) with distinct apo(a) isoforms (e.g. B/S3, S1/S4) were prepared by density gradient ultracentrifugation of plasma, and tested. Lp(a) fractions containing mainly small apo(a) isoforms (either B or S1) showed the highest affinity for fibrin (Kd approximately 150 nmol L-1) and the best competitor activity for plasminogen, whereas fractions containing mainly the high molecular mass isoforms (either S3 or S4) showed the lowest affinities (Kd > or = 500 nmol L-1). An increase in Kd was observed as a function of the relative content in isoforms of high molecular mass in these fractions. This inverse relationship between affinity for fibrin and apo(a) size indicates that Lp(a) subspecies in heterozygotes may have different pathogenic potential. Thus, the antifibrinolytic effect of Lp(a) in heterozygous subjects would depend on the relative concentration of the isoform with the highest affinity for fibrin.
Hervio
L
L
Institut National de la Santé et de la Recherche Médicale, INSERM U143, Centre Hospitalier Universitaire de Bicêtre, Paris, France.
Girard-Globa
A
A
Durlach
V
V
Anglés-Cano
E
E
D000328:Adult; D000368:Aged; D001054:Apolipoproteins A / Q000097:blood*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D005337:Fibrin; D010958:Plasminogen