β2-glycoprotein I deficiency:

Yasuda, Shinsuke; Tsutsumi, Akito; Chiba, Hitoshi; Yanai, Hidekatsu; Miyoshi, Yukiko; Takeuchi, Rie; Horita, Tetsuya; Atsumi, Tatsuya; Ichikawa, Kenji; Matsuura, Eiji; Koike, Takao

doi:10.1016/s0021-9150(99)00496-7

Cited by 72 publications

(10 citation statements)

References 36 publications

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“…They suggest that high levels of beta(2)-GPI-Lp(a) are associated with the presence and severity of CAD and may be a strong risk factor for atherosclerosis. An association in APS patients was shown as well [40]. This should be object of further research.…”

Section: Discussionmentioning

confidence: 79%

“…Yasuda et al [40] focussed on the association of beta(2)-GPI and lipoprotein metabolism in APS patients, they showed individuals with heterozygous beta(2)-GPI deficiency showed significantly lower concentrations of serum beta(2)-GPI, but no significant influence on lipid metabolism was found.…”

Section: Resultsmentioning

confidence: 99%

“…Oxidation of LDL and Lp(a) is postulated to play a key role in the early initiation of atherosclerosis. Also changes in lipoproteins due to glycosylation, like the formation of beta(2)-GPI-Lp(a) [26] which were first detected in patients with RA and APS [28, 40, 41], and then in patients with CAD [42], might lead to early atherosclerosis. …”

Section: Discussionmentioning

confidence: 99%

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A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis

Missala

Kassner

Steinhagen‐Thiessen

2012

International Journal of Rheumatology

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Objective. To investigate the association of lipoprotein(a) and atherosclerosis-related autoimmune diseases, to provide information on possible pathophysiologic mechanisms, and to give recommendations for Lp(a) determination and therapeutic options. Methods. We performed a systematic review of English language citations referring to the keywords “Lp(a)” AND “autoimmune disease” AND “atherosclerosis,” “Lp(a)” AND “immune system” OR “antiphospholipid (Hughes) syndrome (APS)” OR “rheumatoid arthritis” OR “Sjögren's syndrome” OR “systemic lupus erythematosus” OR “systemic sclerosis” OR “systemic vasculitis” published between 1991 and 2011 using Medline database. Results. 22 out of 65 found articles were identified as relevant. Lp(a) association was highest in rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE), moderate in APS and lowest in systemic sclerosis (SSc). There was no association found between Lp(a) and systemic vasculitis or Sjögren's syndrome. Conclusion. Immune reactions are highly relevant in the pathophysiology of atherosclerosis, and patients with specific autoimmune diseases are at high risk for CVD. Elevated Lp(a) is an important risk factor for premature atherosclerosis and high Lp(a) levels are also associated with autoimmune diseases. Anti-Lp(a)-antibodies might be a possible explanation. Therapeutic approaches thus far include niacin, Lp(a)-apheresis, farnesoid x-receptor-agonists, and CETP-inhibitors being currently under investigation.

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Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

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A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis

Missala

Kassner

Steinhagen‐Thiessen

2012

International Journal of Rheumatology

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“…Yasuda et al [136] identified and reported 2 Japanese families with β2GPI deficiency due to a single mutation deletion. Notwithstanding the multiple functions of β2GPI, its genetic deficiency does not represent a risk factor for coagulation disorders like thrombosis or excessive bleeding in humans [137].…”

Section: Binding Of Anticardiolipin Antibodies To 2gpimentioning

confidence: 99%

Some Recent Insights into the Prothrombogenic Mechanisms of Antiphospholipid Antibodies

Todorova¹,

Baleva

2007

CMC

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Antiphospholipid antibodies (aPL) are a heterogeneous group of autoantibodies, detected in the sera of patients with both autoimmune and various non-autoimmune diseases. They are also detected in subjects with no overt underlying disease - the primary antiphosphilipid syndrome (PAPS). High titers of APL are associated with arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia. There have been many suggestions explaining the potential mechanisms of the procoagulant effect of aPL. These include endothelial cell (EC) activation; increased adhesion molecule expression; inhibition of EC prostacyclin release, increased leucocyte adhesion to EC, downregulation of thrombomodulin expression. APL induce the procoagulant activity of monocytes via increased tissue factor expression and directly stimulate platelet hyperactivity with resultant production of enhanced amounts of the proaggregatory molecule of TXA(2). In vitro studies show that prepro-endothelin-1 mRNA is induced by human monoclonal anticardiolipin antibodies and this might contribute to vasospasm, and, ultimately, to arterial occlusion. The hypercoagulable state in APS patients is associated with alterations in the protein C/S pathway. It is suggested that aPL may impair the protein C anticoagulant system. Acquired protein C and protein S deficiency is described in patients with APS. Beta2- glycoprotein I, (Beta2-GPI) a natural anticoagulant, is involved in the regulation of protein S anticoagulant activity by preventing the binding of protein S to C4b-binding protein. APL were shown to inhibit this effect of Beta2- GP I. As the group of aPL is very heterogeneous, it is unlikely that a single mechanism is responsible for the thrombogenic activity of all aPLs associated with thrombosis.

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“…The functions of β 2 -GPI are involved in a variety of physiological processes including triglyceride metabolism, vascular homeostasis, and blood coagulation [4,5]. Our previous studies demonstrated that β 2 -GPI induces endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production through the NF-κB signaling pathway, thereby modulating vascular cell migration [6].…”

Section: Introductionmentioning

confidence: 99%

β2-Glycoprotein I Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis by Suppressing the Phosphorylation of Extracellular Signal-Regulated Kinase 1/2, Akt, and Endothelial Nitric Oxide Synthase

et al. 2016

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Angiogenesis is the process of new blood vessel formation, and it plays a key role in various physiological and pathological conditions. The β2-glycoprotein I (β2-GPI) is a plasma glycoprotein with multiple biological functions, some of which remain to be elucidated. This study aimed to identify the contribution of 2-GPI on the angiogenesis induced by vascular endothelial growth factor (VEGF), a pro-angiogenic factor that may regulate endothelial remodeling, and its underlying mechanism. Our results revealed that β2-GPI dose-dependently decreased the VEGF-induced increase in endothelial cell proliferation, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and the bromodeoxyuridine (BrdU) incorporation assays. Furthermore, incubation with both β2-GPI and deglycosylated β2-GPI inhibited the VEGF-induced tube formation. Our results suggest that the carbohydrate residues of β2-GPI do not participate in the function of anti-angiogenesis. Using in vivo Matrigel plug and angioreactor assays, we show that β2-GPI remarkably inhibited the VEGF-induced angiogenesis at a physiological concentration. Moreover, β2-GPI inhibited the VEGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, and endothelial nitric oxide synthase (eNOS). In summary, our in vitro and in vivo data reveal for the first time that β2-GPI inhibits the VEGF-induced angiogenesis and highlights the potential for β2-GPI in anti-angiogenic therapy.

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β2-glycoprotein I deficiency:

Cited by 72 publications

References 36 publications

A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis

A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis

Some Recent Insights into the Prothrombogenic Mechanisms of Antiphospholipid Antibodies

β2-Glycoprotein I Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis by Suppressing the Phosphorylation of Extracellular Signal-Regulated Kinase 1/2, Akt, and Endothelial Nitric Oxide Synthase

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