Angiopoietin-Like Proteins 4 ( ANGPTL4 ) Gene Polymorphisms and Risk of Brain Arteriovenous Malformation

Erkinova, Sarafroz A.; Соколова, Е. А.; Orlov, Kirill; Kiselev, Vitaly S.; Strelnikov, N; Dubovoy, A. V.; Воронина, Е. Н.; Филипенко, М. Л.

doi:10.1016/j.jstrokecerebrovasdis.2017.10.033

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…In these papers, 14 single nucleotide polymorphisms (SNPs) in 10 genes (rs2071219,10–14 rs706819,11 14 and rs1116995311 14 in ACVRL1 ; rs1154566410–12 and rs1098775910 11 in ENG ; rs180079512 15 in IL6 ; rs114362712 13 15 16 and rs1694412 15–17 in IL1B ; rs52261613 16 18 in MMP3 ; rs1167243316 19 20 in ANGPTL4 ; rs302501016 21 in VEGFA ; rs180058713 22 in IL1A ; rs701556616 23 in GPR124 ; and rs133304016 24 25 in CDKN2B-AS1 ) from 16 candidate gene association studies were evaluated for further meta-analysis. These studies were performed mainly in Caucasian and Asian populations.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to CDKN2B-AS1 , a prominent impact of neuroinflammation involving NFĸB signaling has been described in bAVM, and particularly rupture of the AVM. Genetic polymorphisms coding for inflammation related molecules, such as IL-1, IL-6, VEGF, MMP-3, and ANGPTL4, have been tested in association studies, and several SNPs have been identified in different populations 12 13 15–17 19 20. Although these inflammatory genes have been shown to be associated with vascular diseases in genetic studies or with bAVM in experimental studies, evidence of association of SNPs in these genes were not identified after analysis (table 1).…”

Section: Discussionmentioning

confidence: 99%

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Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation

Liu

Zhang

et al. 2022

J NeuroIntervent Surg

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BackgroundThe pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in bAVM. This study examined genetic variants associated with bAVM through quantitative synthesis and qualitative description of literature.MethodsFive databases were searched to gather potentially relevant articles published up to January 2022. STATA 14.0 software was used for statistical analyses. Pooled odds ratios and 95% confidence intervals were calculated with random effect models, and heterogeneity was assessed using the Cochran Q test and quantified with the I2 test. Sensitivity and publication bias were analyzed to test the robustness of the associations. Variants identified in only one study or with great heterogeneity were not suitable for pooling association analysis, and therefore a qualitative systematic review was performed.ResultsIn total, 30 papers were included in a systematic review involving 4709 cases and 7832 controls, where 17 papers were in a meta-analysis. A suggested association of bAVM was observed with ACVRL1 rs2071219 in the additive model and CDKN2B-AS1 rs1333040 in the recessive and additive models. Other variants of genes that could not be analyzed were summarized by qualitative description. These genes were mostly involved in bone morphogenic protein/transforming growth factor beta (BMP/TGF-β), vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), and RAS-mitogen activated protein kinase (MAPK) signaling and inflammation.ConclusionsAccording to our meta-analysis, ACVRL1 rs2071219 and CDKN2B-AS1 rs1333040 were potentially associated with bAVM. Multiple pathological signaling pathways could affect disease development. Future studies should aim to determine the interaction of candidate genes with environmental risk factors and to elucidate detailed mechanisms of action of variants and genes.1

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation

Liu

Zhang

et al. 2022

J NeuroIntervent Surg

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“…GPR124 was predicted as a potential target of miR-138-5p by Target scan. GPR124 functionally promotes physiological embryonic and angiogenesis within the central nervous system [26,27]. We focused on GPR124 because of its established relevance in angiogenesis and atherosclerosis possibly related to embryo implantation.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Associated MicroRNA-138-5p Regulates Embryo Implantation and Early Pregnancy by Adjusting GPR124

Tsai

et al. 2022

Pharmaceutics

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Functional embryo–maternal interactions occur during the embryo implantation and placentation. Extracellular vesicles with microRNA (miR) between cells have been considered of critical importance for embryo implantation and the programming of human pregnancy. MiR-138-5p functions as the transcriptional regulator of G protein-coupled receptor 124 (GPR124). However, the signaling pathway of miR138-5p- and GPR124-adjusted NLRP3 inflammasome activation remains unclear. In this study, we examine the roles of the miR138-5p and GPR124-regulated inflammasome in embryo implantation and early pregnancy. Human decidual stromal cells were isolated from the abortus tissue and collected by curettage from missed abortion patients and normal pregnant women at 6– to 12-week gestation, after informed consent. Isolated extracellular vesicles from decidua and decidual stromal cells were confirmed by transmission electron microscopy (TEM). Next-Generation Sequencing (NGS) and microarray were performed for miR analysis. The predicated target genes of the differentially expressed miR were analyzed to identify the target genes and their pathway. We demonstrated the down-regulation of miR-138-5p and the overexpression of GPR124 in spontaneous miscarriage compared to normal pregnancy. We also showed the excessive activation of the NLRP3 inflammasome in spontaneous miscarriage compared to normal pregnancy. Here, we newly demonstrate that the miR-138-5p and GPR124-adjusted NLRP3 inflammasome were expressed in extracellular vesicles derived from decidua and decidual stromal cells, indicating that the miR-138-5p, GPR124 and NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome have a potential modulatory role on the decidual programming and placentation of human pregnancy. Our findings represent a new concept regarding the role of extracellular vesicles, miR-138-5p, GPR124, and the NLRP3 inflammasome in normal early pregnancy and spontaneous miscarriage.

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“…GPR124 (probable G-protein coupled receptor 124) was predicted as a potential target of miR-138-5p by Target scan. GPR124 is an orphan G protein-coupled receptor that functionally promotes physiological embryonic and angiogenesis within the central nervous system [24,25]. We focused on GPR124 because of its established relevance in angiogenesis and atherosclerosis possibly related to embryo implantation.…”

Section: Discussionmentioning

confidence: 99%

“…Fold regulation and fold change in miRNA dataset were obtained upon the normalization by geNorm method. It has been determined that the results of cross multiple prediction algorithms can increase speci city, and decrease sensitivity [24]. Hence, we chose to integrate the results of the bioinformatics prediction programs TargetScan 7.2 (http://www.targetscan.org) and MiRDB (http://mirdb.org/miRDB/).…”

Section: Qiaseq Mirna Data Analysis and Target Gene Predictionmentioning

confidence: 99%

Extracellular vesicle-associated microRNA-138-5p regulates embryo implantation and early pregnancy by adjusting GPR124

Tsai

et al. 2022

Preprint

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Background Functional embryo-maternal interactions occur during the embryo implantation and placentation. Extracellular vesicles with microRNA (miRNA) between cells have been considered of critical importance for embryo implantation and programming of human pregnancy. MicroRNA-138-5p functions as the transcriptional regulator of GPR124. However, the mechanism of microRNA-138-5p- and GPR124-regulated NLRP3 inflammasome activation remains unclear. In this study, we examine the roles of microRNA-138-5p and GPR124-regulated inflammasome in embryo implantation and early pregnancy. Methods Human decidual stromal cells were isolated from the abortus tissue, collected by curettage from missed abortion patients and normal pregnant women at 6- to 12-wk gestation, after informed consent. Transmission electron microscopy (TEM) images of isolated extracellular vesicles were obtained. NGS and microarray were performed for miRNAs analysis. The predicated target genes of the differentially expressed miRNA were analyzed to identify the target genes and their pathway. Results Isolated extracellular vesicles from decidua and decidual stromal cells were confirmed by TEM images. We demonstrated the down-regulation of miR-138-5p and the overexpression of GPR124 in spontaneous miscarriage compared to normal pregnancy. We also showed the excessive activation of NLRP3 inflammasome in spontaneous miscarriage compared to normal pregnancy. Conclusions Here we newly demonstrate that the miR-138-5p and GPR124-regulated NLRP3 inflammasome were expressed in extracellular vesicles derived from decidua and decidual stromal cells, indicating the miR-138-5p, GPR124 and NLRP3 inflammasome have potential modulatory role on decidual programming and placentation of human pregnancy. Our findings represent a new concept regarding the role of extracellular vesicles, miR-138-5p, GPR124, and NLRP3 inflammasome in normal early pregnancy and spontaneous miscarriage.

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Angiopoietin-Like Proteins 4 ( ANGPTL4 ) Gene Polymorphisms and Risk of Brain Arteriovenous Malformation

Cited by 12 publications

References 13 publications

Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation

Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation

Extracellular Vesicle-Associated MicroRNA-138-5p Regulates Embryo Implantation and Early Pregnancy by Adjusting GPR124

Extracellular vesicle-associated microRNA-138-5p regulates embryo implantation and early pregnancy by adjusting GPR124

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