Identification of mechanisms that may modulate the role of lipoprotein(a) in thrombosis and atherogenesis.
In this report, we review recent findings concerning the identification of mechanisms that may modulate the role of lipoprotein(a), or Lp(a), in thrombosis and atherogenesis. Lp(a) binds to surface-immobilized plasmin-modified fibrin, thus providing a mechanism for incorporating Lp(a) into the vessel wall. We found that homocysteine and other sulfhydryl-containing amino acids markedly increase the binding of Lp(a) to plasmin-modified fibrin. Our results suggest that homocysteine alters the structure of Lp(a) to expose lysine-binding sites on the apolipoprotein(a) portion of the molecule, and thus provide a potential biochemical link between thrombosis and atherogenesis. We also found that transglutaminases catalyze the incorporation of primary amines into Lp(a). Studies in cell culture systems have found that Lp(a) stimulates endothelial cells to synthesize and release plasminogen activator inhibitor-1. Further, Lp(a) inhibits the activation of transforming growth factor-beta in a coculture of bovine endothelial and smooth muscle cells.
Division of Hematology, Mount Sinai School of Medicine, New York, NY 10029.
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D000603:Amino Acids, Sulfur / Q000502:physiology; D001161:Arteriosclerosis / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D005337:Fibrin / Q000502:physiology; D006801:Humans; D017270:Lipoprotein(a) / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*; D011503:Transglutaminases / Q000502:physiology
D000603:Amino Acids, Sulfur; D017270:Lipoprotein(a); D005337:Fibrin; D011503:Transglutaminases