Immunolocalization of beta(2) glycoprotein I (apolipoprotein H) to human atherosclerotic plaques - Potential implications for lesion progression

Backgronnd-beta(2)-Glycoprotein I (beta 2GPI) is a major antigenic target o f antiphospholipid antibodies, which possesses natural anticoagulant proper ties. The aim of the present study was to determine its presence and locali zation within human atherosclerotic plaques and to study its association wi th endothelial cells and monocyte macrophages in vitro. Methods and Results-Human atherosclerotic lesions were obtained after carot id endarterectomies and studied immunohistochemically with anti-beta 2GPI a s well as antibodies to CD4/CD8, macrophages, and adhesion molecules. In vi tro, human umbilical vein endothelial cells (HUVECs) and U937 (myelomonocyt ic cell line) cells were investigated for their ability to associate with r adiolabeled beta 2GPI. We found beta 2GPI to be abundantly expressed within the subendothelial regions and intimal-medial borders of human atheroscler otic plaques and to colocalize with CD4-positive lymphocytes. This observat ion was confirmed by Western blot applied on homogenates of atherosclerotic lesions with anti-beta 2GPI antibodies. Both HUVECs and U937 cells bound l abeled beta 2GPI, and the process was inhibited by oxidized LDL and not by native LDL. Conclusions-The abundant presence of human beta 2GPI within the lesions, it s association with endothelial cells and macrophages, and its colocalizatio n with CD4-positive lymphocytes suggests that it may serve as a target for an immune-mediated reaction that can influence lesion progression.