A potential basis for the thrombotic risks associated with lipoprotein(a).
Lipoprotein(a) (Lp(a)) has been strongly linked with atherosclerosis and is an independent risk factor for myocardial infarction. Distinguishing Lp(a) from other low-density lipoprotein particles is its content of a unique apoprotein, apo(a). The recently described sequence of apo(a) indicates a remarkable homology with plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin. Lp(a) may contain 37 or more disulphide-looped kringle structures, which are 75-85% identical to the fourth kringle of plasminogen. Plasminogen receptors are widely distributed on blood cells and are present at extremely high density on endothelial cells. These receptors promote thrombolysis by accelerating plasminogen activation and protecting plasmin from inhibition. If, by molecular mimicry, Lp(a) competes with plasminogen for receptors, then thrombolysis would be inhibited and thrombosis promoted. Here we provide support for such a mechanism being responsible for the thrombotic risks associated with elevated Lp(a) by demonstrating that Lp(a) inhibits plasminogen binding to cells.
Miles
L A
LA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Fless
G M
GM
Levin
E G
EG
Scanu
A M
AM
Plow
E F
EF
D001667:Binding, Competitive; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000494:pharmacology / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*
D017270:Lipoprotein(a); D008074:Lipoproteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen