Abstract
Objective
Lipoprotein(a) [Lp(a)] is a risk factor for stroke, as has recently been further confirmed
by meta analysis, and consists of low-density lipoprotein and apolipoprotein(a), which
shares a significant amino acid homology with plasminogen. Oxidized Lp(a) [Ox-Lp(a)]
is a more pathogenic species of Lp(a). A monoclonal antibody, specific to Ox-Lp(a),
distinguishes immunolocalization of Ox-Lp(a) from that of Lp(a) and that of plasminogen
which carries highly homologous domains. It is worth examining their possibly differential
immunolocalizations around atherosclerotic lesions in human carotid and cerebral arteries.
Methods and results
Stage-related differences in immunolocalization of Ox-Lp(a), native Lp(a), and plasminogen
were investigated in various atherosclerotic lesions of the human carotid (obtained
from 13 patients undergoing carotid endarterectomy) and cerebral arteries (from 11
cadavers). Native Lp(a) was seen in the fibrous cap, extracellular matrix, endothelial
cells, and subendothelial layer. Unorganized mural thrombi were positive for plasminogen,
but not Lp(a). In contrast, fibrin deposits in thickened intima were positive for
Lp(a), but not plasminogen. Ox-Lp(a)-like immunoreactivity was seen in endothelial
cells in the early stage of atherosclerosis. Ox-Lp(a) deposition was more abundant
in synthetic phase vascular smooth muscle cells (VSMC) than in contractile phase VSMC.
Conclusion
We demonstrated differential immunoexpression patterns between native Lp(a) and plasminogen,
and suggested that Lp(a)-plasminogen interaction may play a part in differential mechanisms
in all atherosclerotic lesions of human carotid and cerebral arteries. The preferential
presence of Ox-Lp(a) seen in endothelial cells suggests initial dysfunction of endothelial
cells in atherosclerosis. The relative abundance of Ox-Lp(a) in synthetic phase VSMC
is associated with their phenotypic changes during the progression of atherosclerosis.
Abbreviations:
IR (immunoreactivity), Lp(a) (lipoprotein(a)), Ox-Lp(a) (oxidized lipoprotein(a)), Apo(a) (apolipoprotein(a)), t-PA (tissue plasminogen activator), PAI-1 (plasminogen activator inhibitor-1), Lp-PL A2 (lipoprotein-associated phospholipase A2), LPC (lyso-phosphatidylcholine), VSMC (vascular smooth muscle cell), SMA (smooth muscle actin)Keywords
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Article info
Publication history
Published online: February 08, 2011
Accepted:
October 7,
2010
Received in revised form:
September 14,
2010
Received:
May 6,
2010
Identification
Copyright
© 2011 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
