(Circulation. 1999;99:2227-2230.)
© 1999 American Heart Association, Inc.
Brief Rapid Communication |
Immunolocalization of ß2-Glycoprotein I (Apolipoprotein H) to Human Atherosclerotic Plaques
Potential Implications for Lesion Progression
From the Research Unit of Autoimmune Diseases (J.G., B.G., Y.L., Y.S.), Department of Medicine B; Institute of Lipid and Atherosclerosis Research (D.H.), Institute of Pathology (A.A., I.B., J.K.); and Department of Vascular Surgery (J.S.), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Background—ß2-Glycoprotein I (ß2GPI) 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-ß2GPI 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 ß2GPI. We found ß2GPI 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-ß2GPI antibodies. Both HUVECs and U937 cells bound labeled ß2GPI, and the process was inhibited by oxidized LDL and not by native LDL.
Conclusions—The abundant presence of human ß2GPI 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.
Key Words: atherosclerosis • glycoproteins • antibodies • lipoproteins
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|
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|
|
|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|