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Title: Dual effect of apolipoprotein(a) on plasm in (ogen)-induced apoptosis through modulation of cell detachment of adherent cells
Authors: Ho-Tin-Noe, B ×
Meilhac, O
Rossignol, P
Lijnen, Roger
Angles-Cano, E #
Issue Date: Jan-2006
Publisher: F.K. Schattauer
Series Title: Thrombosis and Haemostasis vol:95 issue:1 pages:142-150
Conference: date:CHU Bichat Claude Bernard, INSERM, U698, F-75877 Paris, France; Univ Paris Denis Diderot, Paris, France; Katholieke Univ Leuven, Ctr Mol & Vasc Biol, Louvain, Belgium
Abstract: Because of its structural homology with plasminogen, the apolipoprotein(a) [apo(a)] component of the athero-thrombogenic lipoprotein(a) [Lp(a)] particle inhibits plasminogen binding and activation onto fibrin as well as the subsequent fibrinolysis. In a similar manner, apo(a) may also interfere with plasmin(ogen)induced cell detachment and apoptosis of adherent cells. To investigate this hypothesis, we studied the effect of a recombinant apo(a) [r-apo(a)] on plasminogen activation-induced apoptosis of vascular smooth muscle cells (VSMCs) and fibroblasts-like CHO-KI cells. We demonstrate for the first time that apo(a) displays a concentration-dependent biphasic, enhancing/preventing effect on plasmin(ogen) induced cell detachment of VSMCs and CHO-KI cells. Our results show that r-apo(a) binds to these cells with higher affinity than plasminogen [K-d = 0.9 +/- 0.2 mu M for plasminogen, K-d = 1.77 +/- 0.34 nM for r-apo(a)] in a lysine-dependent manner. At high r-apo(a)/plasminogen ratios, their competitive interaction results in a partial inhibition of plasminogen activation by cell-bound t-PA. As a consequence, r-apo(a) prevents plasm in (ogen)-induced cell detachment and apoptosis. Surprisingly, at low r-apo(a)/plasminogen ratios,an enhancement in plasm in (ogen)-induced cell detachment and apoptosis was observed. This effect was shown to be "plasmin-selective" as r-apo(a) was unable to potentiate cell detachment induced by human neutrophil elastase and trypsin. Altogether these data are consistent with a new mechanism of apo(a)/plasmin(ogen) interactions that may contribute to the atherothrombogenic potential of Lp(a).
ISSN: 0340-6245
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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