The involvement of beta2-glycoprotein I (beta2-GPI) in human and murine atherosclerosis.
Atherosclerosis is a multifactorial process, the hallmark of which is fat deposition in the vessel wall. Autoimmune factors have recently been shown to play an important role in the initiation and progression of atherosclerosis; candidate autoantigens are oxidized lipids and heat shock proteins. beta2-glycoprotein I (beta2-GPI) is a highly glycosylated plasma protein that serves as a major antigenic target for autoimmune type antiphospholipid antibodies. Its major relevant property is binding to negatively charged phospholipids/surfaces. In the set of studies presented in this paper, we provide evidence pointing towards beta2-GPI as an influential determinant in murine and human atherogenesis. Thus, immunization of transgenic atherosclerosis-prone mice (apolipoprotein E and low-density lipoprotein receptor knockouts) with human beta2-GPI results in a brisk and sustained respective response that extends to cross-react with the 'self' murine beta2-GPI. Atherosclerosis is accelerated in both strains concomitant with the infiltration of CD4 lymphocytes in the aortic sinus of the mice. When human plaques were studied, it was found that beta2-GPI resides in the subendothelial regions and co-localizes with CD4 lymphocytes. Thus, the immune response towards beta2-GPI may play an important role in atherogenesis, serving as a possible target for antigen specific therapies.
George
J
J
Department of Medicine 'B' and the Research Unit of Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Shoenfeld
Y
Y
Harats
D
D
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D001324:Autoantigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D020298:U937 Cells; D053482:beta 2-Glycoprotein I
D001057:Apolipoproteins E; D001324:Autoantigens; D006023:Glycoproteins; D011973:Receptors, LDL; D053482:beta 2-Glycoprotein I