Anti-phospholipid Antibodies Increase Non-apoptotic Trophoblast Shedding: A Contribution to the Pathogenesis of Pre-eclampsia in Affected Women?

Chen, Qi; Viall, Chez A.; Kang, Yu; Liu, Bonnia; Stone, Peter; Chamley, Larry

doi:10.1016/j.placenta.2009.06.008

Cited by 45 publications

(37 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endosomal signaling appears likewise to be important for the wellknown role of reactive oxygen species in the induction of TF expression induced by aPLA [30]. In addition, aPLA were localized within the shed syncytial knots and in the syncytiotrophoblast of the aPLA-treated explants [49]. In this context, chlorpromazine and hydroxychloroquine are used for the treatment of schizophrenia, malaria, lupus erythematous and rheumatic disorders [50].…”

Section: Discussionmentioning

confidence: 99%

NF‐κB is activated from endosomal compartments in antiphospholipid antibodies‐treated human monocytes

Brandt

Fickentscher

Boehlen

et al. 2014

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

To cite this article: Brandt KJ, Fickentscher C, Boehlen F, Kruithof EKO, de Moerloose P. NF-jB is activated from endosomal compartments in antiphospholipid antibodies-treated human monocytes. J Thromb Haemost 2014; 12: 779-91.See also Groot PG, Urbanus RT. Cellular signaling by antiphospholipid antibodies. This issue, pp 773-5 and Gris JC. The hidden activism of the misnamed. This issue, pp 776-8.Summary. Background: The antiphospholipid antibody syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). We recently demonstrated that Toll-like receptor 2 (TLR2) and CD14 contribute to monocyte activation of aPLA. Objective: To study the mechanisms of cell activation by aPLA, leading to pro-coagulant and pro-inflammatory responses. Methods and Results: For this study, we used purified antibodies from the plasmas of 10 different patients with APS and healthy donors. We demonstrate that aPLA, but not control IgG, co-localizes with TLR2 and TLR1 or TLR6 on human monocytes. Blocking antibodies to TLR2, TLR1 or TLR6, but not to TLR4, decreased TNF and tissue factor (TF) responses to aPLA. Pharmacological and siRNA approaches revealed the importance of the clathrin/dynamin-dependent endocytic pathway in cell activation by aPLA. In addition, soluble aPLA induced NF-jB activation, while bead-immobilized aPLA beads, which cannot be internalized, were unable to activate NF-jB. Internalization of aPLA in monocytes and NF-jB activation were dependent on the presence of CD14. Conclusion: We show that TLR2 and its co-receptors, TLR1 and TLR6, contribute to the pathogenicity of aPLA, that aPLA are internalized via clathrin-and CD14-dependent endocytosis and that endocytosis is required for NF-jB activation. Our results contribute to a better understanding of the APS and provide a possible therapeutic approach.

show abstract

Section: Discussionmentioning

confidence: 99%

NF‐κB is activated from endosomal compartments in antiphospholipid antibodies‐treated human monocytes

Brandt

Fickentscher

Boehlen

et al. 2014

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…According to some recent research, aPL can cause placenta insufficiency by adversely affecting trophoblast viability, syncytialization, and invasion. aPL can promote trophoblast apoptosis by altering the expressions of apoptotic regulators (Bax and Bcl‐2) or could result in abnormal death by regulating cell cycle . Syncytialization could be disturbed for that aPL can suppress the expression of initiator caspases to disturb the fusion of cytotrophoblasts .…”

Section: Introductionmentioning

confidence: 99%

“…12 Syncytialization could be disturbed for that aPL can suppress the expression of initiator caspases to disturb the fusion of cytotrophoblasts. 12 For trophoblast invasion, it can be reduced because of the down-regulation of α1 integrin and VE-cadherin, both of which promote cytotrophoblast invasiveness, 13 and the diminished expression of matrix metalloproteinases 14 caused by aPL. Besides, it is reported that aPL also can trigger inflammation of trophoblastic tissues 15 and result in pro-inflammatory changes in the vascular wall, causing a pro-thrombotic state and placenta insufficiency, which is associated with obstetric complications.…”

Section: Introductionmentioning

confidence: 99%

Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: A systematic review and network meta‐analysis

Liu

Qiu

et al. 2020

American J Rep Immunol

View full text Add to dashboard Cite

Antiphospholipid syndrome (APS) is one of the treatable causes for pregnant women with recurrent pregnancy loss (RPL). This review compares the efficacy of a few treatment interventions (low‐dose aspirin (LDA), aspirin plus low molecular weight heparin (LMWH), or unfractionated heparin (UFH)) in preventing complications during pregnancy and miscarriages for women with RPL and APS, and the potential differences in therapeutic effects of UFH and LMWH when combined with aspirin. We searched randomized controlled trials (RCTs) in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials and performed a systematic review and a Bayesian network meta‐analysis (NMA). Finally, we found aspirin alone had a lower live birth rate compared to LMWH plus aspirin (OR = 0.37; 95% CrI, 0.17, 0.71), and UFH plus aspirin showed a higher live birth rate than aspirin alone (OR = 2.63; 95% CrI, 1.04, 5.39) in NMA, treating with UFH plus aspirin or LMWH plus aspirin did not have difference on live birth. Furthermore, LDA alone resulted in a lower birthweight compared to heparin plus aspirin, while higher birthweight was found when compared UFH plus aspirin to LMWH plus aspirin (MD = 895.40; 95% CrI, 817.40, 988.57) in NMA. Additionally, in women with RPL and APS and without a prior thrombosis, heparin plus aspirin improved birthweight but could not promote live birth rate compared to aspirin alone. In conclusion, heparin plus aspirin is recommended for women with RPL and APS. Notably UFH plus aspirin demonstrates the most significant therapeutic efficacy among these interventions in improving birthweight.

show abstract

“…Several in vitro studies have reported an increase in trophoblast death in response to aPL using either term trophoblasts or first-trimester trophoblasts (Di Simone et al 2001, Yacobi et al 2002, Ornoy et al 2003, Schwartz et al 2007, Chen et al 2009, Mulla et al 2009). Cytotrophoblasts isolated from term placentae (Di Simone et al 2001 have been shown to alter their expression of the apoptotic regulators Bax and Bcl2 in response to aPL, but without overt signs of cell death (Di Simone et al 2006).…”

Section: Trophoblast Deathmentioning

confidence: 99%

“…Once inside the syncytiotrophoblast, aPL bind to mitochondria and disrupt mitochondrial function and also induce the release of proapoptotic cytochrome c from the mitochondria (Viall et al 2013, Pantham et al 2015a. Consequently, there is an increase in the number of SNAs extruded from the syncytiotrophoblast (Chen et al 2009, Pantham et al 2015a. The proteome of SNAs from aPL-treated placentae is altered compared with that of SNAs from control antibody-treated placentae with notable changes in mitochondria-related proteins (Pantham et al 2015a).…”

Section: Trophoblast Deathmentioning

confidence: 99%

The role of anti-phospholipid antibodies in autoimmune reproductive failure

2016

View full text Add to dashboard Cite

Anti-phospholipid antibodies (aPL) are autoantibodies that are associated with thrombosis and a range of pregnancy complications including recurrent pregnancy loss and pre-eclampsia. The three clinically relevant, well-characterized aPL are anti-cardiolipin antibodies, lupus anticoagulant and anti-beta-2-glycoprotein I (β 2 GPI) antibodies. aPL do not bind directly to phospholipids but instead bind to a plasma-binding 'cofactor'. The most extensively studied cofactor is β 2 GPI, whose role in pregnancy is not fully elucidated. Although the pathogenicity of aPL in recurrent pregnancy loss is well established in humans and animal models, the association of aPL with infertility does not appear to be causative. aPL may exert their detrimental effects during pregnancy by directly binding trophoblast cells of the placenta, altering trophoblast signalling, proliferation, invasion and secretion of hormones and cytokines, and by increasing apoptosis. Heparin is commonly used to treat pregnant women with aPL; however, as thrombotic events do not occur in the placentae of all women with aPL, it may exert a protective effect by preventing the binding of aPL to β 2 GPI or by acting through non-thrombotic pathways. The aim of this review is to present evidence summarizing the current understanding of this field.Reproduction (2016) 151 R79-R90

show abstract

Anti-phospholipid Antibodies Increase Non-apoptotic Trophoblast Shedding: A Contribution to the Pathogenesis of Pre-eclampsia in Affected Women?

Cited by 45 publications

References 33 publications

NF‐κB is activated from endosomal compartments in antiphospholipid antibodies‐treated human monocytes

NF‐κB is activated from endosomal compartments in antiphospholipid antibodies‐treated human monocytes

Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: A systematic review and network meta‐analysis

The role of anti-phospholipid antibodies in autoimmune reproductive failure

Contact Info

Product

Resources

About