Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The involvement of beta2-glycoprotein I (beta2-GPI) in human and murine atherosclerosis. 1044 Nov 68

The antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity in the presence of autoantibodies that recognize beta2-glycoprotein I (beta2GPI) bound to phospholipids. We have previously demonstrated that dimerization of beta2GPI by autoantibodies induces platelet activation, involving the platelet receptor apolipoprotein E receptor 2' (apoER2') a receptor belonging to the low-density lipoprotein receptor (LDL-R) family. Here, we show that dimeric beta2GPI, but not monomeric beta2GPI, interacts with four other LDL-R family members: the LDL-R related protein (LRP), megalin, the LDL-R and the very-low density lipoprotein receptor (VLDL-R). Interaction between dimeric beta2GPI and LDL-R, apoER2' and VLDL-R was best described with a one-site binding model (half-maximal binding; approximately 20 nm for apoER2' and VLDL-R and approximately 300 nm for LDL-R), whereas the interaction between dimeric beta2GPI and LRP or megalin was best described with a two-site binding model, representing a high- (approximately 3 nm) and a low-affinity site (approximately 0.2 microm). Binding to all receptors tested was unaffected by a tryptophane to serine (W316S) substitution in domain V of beta2GPI, which is known to disrupt the phospholipid binding site of beta2GPI. Also deletion of domain I or II left the interaction with the receptors unaffected. Deletion of domain V, however, significantly decreased the affinity for the receptors. In conclusion, our data show that dimeric beta2GPI can interact with different LDL-R family members. This interaction is dependent on a binding site within domain V of beta2GPI, which does not overlap with the phospholipid-binding site within domain V.
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PMID:Interaction of beta2-glycoprotein I with members of the low density lipoprotein receptor family. 1687 8