Hedgehog lipoprotein(a) is a modulator of activation of plasminogen at the fibrin surface. An in vitro study.
Lipoprotein(a) (Lp[a]), a highly atherogenic lipoprotein particle, is the prominent apolipoprotein B-containing lipoprotein in the hedgehog (Laplaud PM et al, J Lipid Res 1988;29:1157-1170). In the present work, we studied the consequences of the structural homology between the specific Lp(a) glycoprotein, apoprotein(a), and plasminogen on the generation of plasmin by fibrin-bound tissue-type plasminogen activator. The activation of plasminogen was initiated by adding either native plasma or Lp(a)-free plasma supplemented with the equivalent of 0.25 mg/ml of either purified Lp(a) or albumin to a surface of fibrin prepared on micortitration plates and to which human tissue-type plasminogen activator was specifically bound. With the Lp(a)-free plasma, an increase in the binding and activation of plasminogen as a function of time was observed. In contrast, in the presence of Lp(a) (i.e., native plasma or the reconstituted system), a significant decrease in the binding of plasmin(ogen) (approximately 60%) was obtained. These data indicate that hedgehog Lp(a) interferes with the binding and activation of plasminogen at the fibrin surface and may thereby behave as a factor regulating the extent of fibrin deposition. These results support our previous data indicating that high levels of Lp(a) may have antifibrinolytic effects in humans (Rouy D et al, Arterioscler Thromb 1991;11:629-638), are in agreement with the observation that Lp(a) is a risk factor for atherosclerotic disease, and provide further support to the view of Lp(a) as a link between atherosclerosis and thrombosis.
Rouy
D
D
Institut National de la Santé et de la Recherche Médicale (INSERM) U. 143, Hôpital de Bicêtre, France.
Laplaud
P M
PM
Saboureau
M
M
Anglés-Cano
E
E
D000327:Adsorption; D000818:Animals; D001798:Blood Proteins; D005337:Fibrin / Q000378:metabolism / Q000502:physiology*; D006364:Hedgehogs / Q000097:blood*; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000502:physiology*; D008239:Lysine; D008297:Male; D010958:Plasminogen / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology
D001798:Blood Proteins; D017270:Lipoprotein(a); D008074:Lipoproteins; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D008239:Lysine