Modification of lipoprotein(a) by oxidation or desialylation influences its ability to compete with plasminogen for binding to the extracellular matrix.
Lipoprotein (a) [Lp(a)], and to a lesser extent low-density lipoprotein (LDL), have been shown to compete with plasminogen for binding to the extracellular matrix (ECM). Evidence exists that modification of lipoproteins alters their atherogenic properties. Therefore in the present study the effect of modifying Lp(a) and LDL by copper-induced in vitro oxidation on their ability to compete with plasminogen for binding to the ECM was studied. Oxidation of Lp(a) resulted in increased competitiveness for plasminogen binding. This effect was dependent on the Lp(a) concentration used, as well as the extent of oxidation. In the highest Lp(a) concentration used (100 nmol/l apo B100), inhibition of plasminogen binding was further increased with almost 30% compared with native Lp(a). In contrast, oxidation of LDL resulted in an additional inhibition of plasminogen binding of about 10% at all concentrations used. In separate experiments Lp(a) and LDL were modified by neuraminidase treatment. After desialylation a strong tendency for better competitiveness of Lp(a) was observed. Desialylation of LDL had no effect on its ability to compete with plasminogen for binding to the ECM. Modification of the additional and distinguishing apolipoprotein [i.e. apo(a)] in Lp(a) by oxidation and desialylation most likely explains the difference in behaviour of Lp(a) and LDL. It is concluded that modification by oxidation, and to a lesser extent desialylation, increases the anti-fibrinolytic potential of Lp(a).
Department of Clinical Chemistry, University Hospital Utrecht, The Netherlands.
H L
HL
Pekelharing
H A
HA
Kleinveld
P F
PF
Duif
B N
BN
Bouma
H J
HJ
van Rijn
D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D010084:Oxidation-Reduction; D010958:Plasminogen / Q000378:metabolism*
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D010958:Plasminogen; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid