Effects of anti‐β2‐glycoprotein I antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cell line

Ichikawa, Go; Yamamoto, Tatsuo; Chishima, Fumihisa; Nakamura, Asuka; Kuno, S; Murase, Takayuki; Suzuki, Michitaka

doi:10.1111/j.1447-0756.2010.01490.x

Cited by 11 publications

(7 citation statements)

References 29 publications

(34 reference statements)

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“…A study by Di Simone and co-workers suggested that one of the causes of aPL-mediated foetal loss was inhibition of angiogenic factor secretion and direct impairment of the placenta angiogenesis [25]. The possible effects of aPLs include limiting trophoblast migration [26], suppressing placenta growth factor production [27] and also modulation of trophoblast angiogenic factor secretion [28].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level

Asnawi

Mohamad

Manzor

et al. 2019

Preprint

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Obstetric antiphospholipid syndrome is initiated by the action of antiphospholipid antibodies on placenta. The characteristics of APS in pregnancy include vascular thrombosis, inflammation and impairment of trophoblast implantation. MicroRNA (miRNA) expression has been suggested as one of the genetic factors that contribute to the development of this syndrome. miRNAs regulate gene expressions in a vast assortment of cellular biological mechanisms include the development of placental tissue. Hence, further investigation on the regulation of placental miRNA in APS is required. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesized signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation from the qPCR data while retinoblastoma gene (RET), dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.

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Section: Discussionmentioning

confidence: 99%

MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level

Asnawi

Mohamad

Manzor

et al. 2019

Preprint

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“…[6][7][8]30 The major pathogenic mechanisms of adverse pregnancies caused by anti-phospholipid antibodies are a hyperthrombogenic state in the intervillous space due to the damage of endothelial cells caused by anti-phospholipid antibodies, 17 as well as direct damage to chorionic villi during the period of placentation. [13][14][15][16] Taking account of these mechanisms, immunosuppressive therapy in combination with anti-coagulation therapy should be adopted as a treatment option for patients with adverse pregnancies caused by anti-phospholipid antibodies. In fact, some authors pointed out the insufficient efficacy of heparin therapy for such patients.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] As an alternative treatment, the efficacy of combined therapy using adrenal corticosteroid hormone (prednisolone) and low-dose aspirin was initially reported. 12 The major pathogenic mechanisms leading to the diversity of adverse pregnancies are considered to be direct damage to chorionic villi by anti-phospholipid antibodies, [13][14][15][16] as well as the formation of intervillous thrombi. 17 Taking account of these mechanisms for reproductive failures caused by anti-phospholipid antibodies, the application of immunosuppressive therapy in combination with anti-coagulation therapy should be reconsidered as a treatment option.…”

Section: Introductionmentioning

confidence: 99%

Treatment for patients with recurrent fetal losses positive for anti‐cardiolipin beta2 glycoprotein I antibody using Sairei‐to (Chai‐ling‐tang) and low‐dose aspirin

Nonaka

Takahashi

Nonaka

et al. 2018

J of Obstet and Gynaecol

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Aim: Recently, it is widely recognized that positivity for anti-phospholipid antibodies is a causative factor for a range of reproductive failures. Anti-cardiolipin beta2 glycoprotein I antibody (anti-CL-beta2-GPI) is a representative anti-phospholipid antibody, which strongly correlates with the development of thrombotic events and diversity of adverse pregnancies. In this series, we aimed to elucidate effective treatment for patients with recurrent fetal losses positive for anti-CL-beta2-GPI using Japanese-modified Chinese herbal medicine.Methods: Twenty-one patients with recurrent fetal losses who were positive for anti-CL-beta2-GPI were treated with the Japanese-modified Chinese herbal medicine, Sairei-to (Chai-ling-tang), and low-dose aspirin with or without adrenal corticosteroid hormone. Of the 21 patients, the value of anti-CL-beta2-GPI ranged from 1.9 to 3.4 in 10 patients, and it was over 3.5 in 11 patients. Results: Of the 21 patients treated with the current protocol, the pregnancy successfully continued in 17 patients (success rate: 81.0%). Of the four patients who showed repeated abortion, chromosome abnormality of chorionic villi was observed in two; thus, the success rate would be 89.5% (17 of 19 cases) on excluding these cases from the evaluation. Conclusion: The efficacy of the current treatment adopting the modified Japanese version of the Chinese herbal medicine Sairei-to for patients with recurrent fetal losses positive for anti-CL-beta2-GPI was indicated.

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“…The main mechanisms involved in the generation of reproductive failures are considered to be the occurrence of direct damage to the chorionic villi caused by antiphospholipid antibodies during the period of placentation [15][16][17][18], and the formation of thrombi intervillous spaces [19]. Considering these mechanisms, the administration of immune suppressive therapy in combination with anti-coagulation therapy is considered to be a viable treatment option.…”

Section: Discussionmentioning

confidence: 99%

A case of a patient positive for anti-cardiolipin antibodies with recurrent fetal wastage and cerebral infarction who was successfully treated with Sairei-to, low dose aspirin, and heparin

Nonaka¹,

Chihara²,

Ooki³

et al. 2012

OJOG

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We report a successful case of a pregnant female positive for anti-cardiolipin antibodies who experienced two abnormal pregnancies with postpartum cerebral hemispheric infarctions. A 38-year-old female diagnosed as being positive for anti-cardiolipin antibodies was referred to our hospital due to her strong desire to have a baby. The administration of Japanese herbal medicine, Sairei-to, as immunosuppressive therapy, and low dose aspirin, as anti-coagulation therapy, were initiated prior to the patient’s pregnancy. Five months after beginning the treatment, the patient conceived spontaneously. At 34 weeks of gestation, emergency cesarean section was performed due to increasing genital bleeding resulting from coincidental placenta previa and the patient delivered an appropriate-for-date female infant (1970 g). Treatment with Japanese herbal medicine (Sairei-to) and low-dose aspirin is considered to be an effective treatment option for patients positive for anti-phospholipid antibodies with past histories of abnormal pregnancies

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Effects of anti‐β2‐glycoprotein I antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cell line

Abstract: Anti-β2-GPI antibody-positive sera and IgG suppress the production of PlGF from JEG-3 cells. We suggest that the anti-β2-GPI antibodies may suppress PlGF production from trophoblasts and cause the failure of placenta formation and function.

Cited by 11 publications

References 29 publications

MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level

MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level

Treatment for patients with recurrent fetal losses positive for anti‐cardiolipin beta2 glycoprotein I antibody using Sairei‐to (Chai‐ling‐tang) and low‐dose aspirin

A case of a patient positive for anti-cardiolipin antibodies with recurrent fetal wastage and cerebral infarction who was successfully treated with Sairei-to, low dose aspirin, and heparin

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