Immunolocalization of β 2 -Glycoprotein I (Apolipoprotein H) to Human Atherosclerotic Plaques

Abstract

Background —β 2 -Glycoprotein I (β2GPI) is a major antigenic target of antiphospholipid antibodies, which possesses natural anticoagulant properties. The aim of the present study was to determine its presence and localization within human atherosclerotic plaques and to study its association with endothelial cells and monocyte macrophages in vitro. Methods and Results —Human atherosclerotic lesions were obtained after carotid endarterectomies and studied immunohistochemically with anti-β2GPI as well as antibodies to CD4/CD8, macrophages, and adhesion molecules. In vitro, human umbilical vein endothelial cells (HUVECs) and U937 (myelomonocytic cell line) cells were investigated for their ability to associate with radiolabeled β2GPI. We found β2GPI to be abundantly expressed within the subendothelial regions and intimal-medial borders of human atherosclerotic plaques and to colocalize with CD4-positive lymphocytes. This observation was confirmed by Western blot applied on homogenates of atherosclerotic lesions with anti-β2GPI antibodies. Both HUVECs and U937 cells bound labeled β2GPI, and the process was inhibited by oxidized LDL and not by native LDL. Conclusions —The abundant presence of human β2GPI within the lesions, its association with endothelial cells and macrophages, and its colocalization with CD4-positive lymphocytes suggests that it may serve as a target for an immune-mediated reaction that can influence lesion progression.