Oxidative modification of Lp(a) causes changes in the structure and biological properties of apo(a).
We previously showed that oxidative modification converted Lp(a) particles to a form readily recognized by macrophage scavenger receptor(s). This was mediated in part by apo(a) changes indicated by a stronger negative charge protein fragmentation and increased immunoreactivity to monoclonal antibody K07, which also cross-reacted with plasminogen (Pg). The present study demonstrated that the expression of K07 and K09 epitopes of apo(a) increased markedly during time-dependent oxidative modification of Lp(a) by copper ions. Incubation of oxidized Lp(a) with the monocytoid U937 cell line showed that these particles competed more effectively with 125I-type 2 Pg binding to specific cell surface receptors than native Lp(a). This study suggests that oxidative Lp(a) modification causes significant changes in apo(a) conformation, resulting in the enhanced interaction of these particles with macrophage scavenger receptors and Pg binding sites.
Naruszewicze
M
M
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada.
Giroux
L M
LM
Davignon
J
J
D001053:Apolipoproteins / Q000737:chemistry* / Q000378:metabolism; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000209:etiology; D001665:Binding Sites; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D017270:Lipoprotein(a) / Q000737:chemistry* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D015394:Molecular Structure; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D010958:Plasminogen / Q000378:metabolism; D011487:Protein Conformation
D001053:Apolipoproteins; D008054:Lipid Peroxides; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D010958:Plasminogen; D053241:Apoprotein(a)