ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages

Liu, Qingping; Kobayashi, Kazuo; Furukawa, Jun; Inagaki, Jiro; Sakairi, Nobuo; Iwado, Akimasa; Yasuda, Tatsuji; Koike, Takao; Voelker, Dennis R.; Matsuura, Eiji

doi:10.1194/jlr.m20063-jlr200

Cited by 70 publications

(72 citation statements)

References 62 publications

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“…Antiphospholipid Abs are directed against epitopes that include proteins such as b2-glycoprotein I (b2GPI) (4)(5)(6), lipids, and protein-lipid complexes. We have demonstrated that anti-b2GPI autoAbs also recognize oxLDL/b2GPI complexes (4,(7)(8)(9)(10). Further, the in vitro macrophage uptake of oxLDL/b2GPI complexes was significantly increased by IgG anti-b2GPI Abs.…”

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confidence: 75%

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The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

Tabuchi

Inoue

Usui-Kataoka

et al. 2007

Journal of Lipid Research

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C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with b2-glycoprotein I (b2GPI), implicating oxLDL/b2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/b2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/b2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and b2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/b2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/b2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/b2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.-Tabuchi, M., K.

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confidence: 75%

“…Further, the in vitro macrophage uptake of oxLDL/b2GPI complexes was significantly increased by IgG anti-b2GPI Abs. (4,(7)(8)(9)(10) Thus, findings suggesting that IgG antib2GPI auto-Abs may be proatherogenic renewed interest in the immunologic mechanisms participating in atherogenesis (4,11,12).…”

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confidence: 99%

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

Tabuchi

Inoue

Usui-Kataoka

et al. 2007

Journal of Lipid Research

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“…Native LDL is taken up by specific LDL receptor whereas oxLDL is taken up by scavenger receptors [46]. The presence of β2GPI and IgG β2GPI auto-antibodies increases the macrophage uptake of I131-Cu2+-oxLDL in keeping with a proatherogenic role of IgG anti-β2GPI antibodies [47]. The uptake of the immune complexes is likely mediated by macrophage Fcγ receptors rather than scavenger receptors.…”

Section: Monocytes/macrophages and Atherosclerosismentioning

confidence: 90%

Atherosclerosis in Primary Antiphospholipid Syndrome: Summary of Clinical and Pathogenic Evidence

Prj

Matsuura³

et al. 2014

J Clin Exp Cardiolog

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The Antiphospholipid Syndrome (APS) was described in the early '80s as a combination of thrombosis, thrombocytopenia and recurrent miscarriages associated with persistent high titers of Antiphospholipid Antibodies (aPL). In subsequent years, it became apparent that aPL were also associated with premature atherosclerosis in Systemic Lupus Erythematosus (SLE) and more recently in primary APS (PAPS). The studies exploring atherosclerosis in PAPS were heterogeneous in conception and size, but overall, provided enough evidence that Intima Media Thickness (IMT) of carotid arteries and endothelial function are abnormal in PAPS. In keeping with the general view that atherosclerosis is a low grade inflammatory and "auto"immune disorder characterised by oxidative and nitrative stress, several studies have confirmed similar findings in PAPS, though a specific relation with the severity of atherosclerosis is lacking. Given its development at an earlier age than average, atherosclerosis should be taken into account in the overall management of PAPS patients as it may significantly add to the vascular risk.

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“…OxLig-1 (7-ketocholesteryl-9-carboxynonanoate) is a Cu 2þ -derived LDL ligand for b 2 GPI prepared as previously described (Liu et al 2002). Fifty microliter of 100 mg/ml of oxLig-1 in ethanol were adsorbed by evaporation on a plain polystyrene plate (Immulon 2HB) followed by blocking with 1% BSA for 1 h at room temperature and then washed.…”

Section: Measurement Of Igg Anti-b 2 Gpi -Oxlig-1 Antibodiesmentioning

confidence: 99%

“…Of further interest is the knowledge that b 2 GPI binds to Cu 2þ -oxidised LDL (oxLDL) and that macrophages uptake this complex much faster in the presence of an antibody towards oxLDLb 2 GPI (Hasunuma et al 1997). More recently, this concept has been extended to the complex of b 2 GPI with 7-ketocholesteryl-9-carboxynonanoate (oxLig-1), the very oxLDL-derived moiety that binds b 2 GPI (Liu et al 2002). As antibodies towards b 2 GPI-oxLig-1 are associated with arterial thrombosis in APS (Lopez et al 2003) we herein explored whether antibodies towards anti b 2 GPI-oxLig-1 bore any atherogenic potential in primary APS.…”

Section: Introductionmentioning

confidence: 99%

Antibodies Against β₂‐Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

Ames

Alves

Lopez

et al. 2006

Journal of Immunology Research

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To explore whether antibodies against b 2 -glycoprotein I (b 2 GPI) complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: b 2 GPIoxLDL complexes, IgG anti-b 2 GPI-oxLig-1, IgG anti-b 2 GPI-oxLDL antibodies (ELISA), PONa, (para-nitrophenol method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal carotid (IC) by high resolution sonography. b 2 GPI-oxLDL complex was highest in the control group ( p , 0.01), whereas, IgG anti-b 2 GPI-oxLig1 and IgG antib 2 GPI-oxLDL were highest in PAPS ( p , 0.0001). In healthy controls, b 2 GPI-oxLDL complexes positively correlated to IMT of the IC ( p ¼ 0.007) and negatively to PONa after correction for age ( p , 0.03). PONa inversely correlated with age ( p ¼ 0.008). In PAPS, IgG anti-b 2 GPI -oxLig-1 independently predicted PONa ( p ¼ 0.02) and IMT of B ( p ¼ 0.003), CC, ( p ¼ 0.03) and of IC ( p ¼ 0.04). In PAPS, PONa inversely correlated to the IMTof B, CC and IC ( p ¼ 0.01, 0.02 and 0.003, respectively). IgG anti-b 2 GPI-oxLig-1 may be involved in PAPS related atherogenesis via decreased PON activity.

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ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages

Cited by 70 publications

References 62 publications

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

Atherosclerosis in Primary Antiphospholipid Syndrome: Summary of Clinical and Pathogenic Evidence

Antibodies Against β₂‐Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

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ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages

Cited by 70 publications

References 62 publications

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

Atherosclerosis in Primary Antiphospholipid Syndrome: Summary of Clinical and Pathogenic Evidence

Antibodies Against β2‐Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

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Product

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Antibodies Against β₂‐Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome