Oxidized Lp(a) appears early in endothelial cells while native Lp(a) marks later fibrin deposits, a study of carotid and cerebral artery plaques (Atherosclerosis 2011)

Original title: Differential expression of oxidized/native lipoprotein(a) and plasminogen in human carotid and cerebral artery plaques

Atherosclerosis · 21 January 2011 · 6

Umahara T, Uchihara T, Yamada S, Hashimoto T, Akimoto J, Haraoka J, Iwamoto T

This study compared immunolocalization of oxidized Lp(a) [Ox-Lp(a)], native Lp(a), and plasminogen in atherosclerotic lesions from human carotid arteries (13 patients undergoing endarterectomy) and cerebral arteries (11 cadavers). Native Lp(a) was found in the fibrous cap, extracellular matrix, endothelial cells, and subendothelial layer; unorganized mural thrombi stained for plasminogen but not Lp(a), while fibrin deposits in thickened intima stained for Lp(a) but not plasminogen. Ox-Lp(a)-like immunoreactivity appeared in endothelial cells early in atherosclerosis and was more abundant in synthetic-phase than contractile-phase vascular smooth muscle cells. The findings suggest Lp(a)-plasminogen interaction contributes to distinct mechanisms across atherosclerotic lesion stages, with early Ox-Lp(a) in endothelial cells pointing to initial endothelial dysfunction in atherosclerosis.

Original 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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.