Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole

Reith, A.; Booth, Nuala A.; Moore, N. R.; Cruickshank, D.J.; Bennett, Bruce

doi:10.1016/0020-7292(94)90045-0

Cited by 16 publications

(23 citation statements)

References 13 publications

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“…Plasma total PAI activity is mostly PAI-1 activity. Estelles et al (1989) and Reith et al (1993) reported increased plasma PAI-1 activity in hypertensive pregnant women. Although we did not assess PAI-1 activity in our subjects, our observation suggests that the increased plasma levels of PAI-1 in the patient with preeclampsia is, at least in part, genetically influenced by the PAI-1 gene polymorphism, and that the 4G allele of the PAI-1 gene may be one of the genetic risk factors for preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…PAI-1, which is a fast-acting inhibitor of t-PA, regulates the rate of clot dissolution (Pannekoek et al 1986). A significant elevation of plasma and placental PAI-1 levels has been found in pregnant woman with severe preeclampsia as compared with levels in normal pregnant women (Estelles et al 1989;Reith et al 1993). A decrease in plasma fibrolytic activity caused by increased PAI-1 levels has also been reported in preeclampsia (Estelles et al 1989;Caron et al 1991;Estelles et al 1994).…”

Section: Introductionmentioning

confidence: 99%

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The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia

et al. 2000

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Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P ϭ 0.04) or in the healthy volunteers (P ϭ 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P ϭ 0.03) and in the healthy volunteers (P ϭ 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia

et al. 2000

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“…17 PAI-1 is expressed in adipose tissue, and its levels are increased in obesity. 18 In pregnancies affected by hypertension, including preeclampsia and HELLP syndrome (hemolysis elevated liver enzymes and low platelet), placental PAI-1 expression 19 and circulating PAI-1 levels [20][21][22][23][24] are increased.…”

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confidence: 99%

Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy

et al. 2016

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Abstract-The risk of developing pregnancy-induced hypertension and preeclampsia is higher in obese pregnant women.In obesity, the composition of the gut microbiota is altered. Obesity is also associated with low-grade inflammation.Metabolites from the gut microbiota may contribute to both hypertension and inflammation. The aim of this study is to investigate whether the composition of the gut microbiota in overweight and obese pregnant women is associated with blood pressure and levels of plasminogen activator inhibitor-1. The composition of the gut microbiota was determined with 16S ribosomal RNA sequencing in 205 women at 16 weeks gestation from the SPRING study (the Study of Probiotics in Gestational Diabetes). Expression of butyrate-producing genes in the gut microbiota was assessed by realtime polymerase chain reaction. Plasminogen activator inhibitor-1 levels were measured in fasting serum of a subset of 70 women. Blood pressure was slightly but significantly higher in obese compared with overweight women. The abundance of the butyrate-producing genus Odoribacter was inversely correlated with systolic blood pressure. Butyrate production capacity was decreased, but plasminogen activator inhibitor-1 concentrations increased in obese pregnant women. Plasminogen activator inhibitor-1 levels were inversely correlated with expression of butyrate kinase and Odoribacter abundance. This study shows that in overweight and obese pregnant women at 16 weeks gestation, the abundance of butyrate-producing bacteria and butyrate production in the gut microbiota is significantly negatively associated with blood pressure and with plasminogen activator inhibitor-1 levels. Increasing butyrate-producing capacity may contribute to maintenance of normal blood pressure in obese pregnant women. Gomez-Arango et al Blood Pressure and Gut Microbiome Butyrate Production 975The SCFA butyrate is produced from dietary fiber by bacteria in the gastrointestinal lumen. There are 2 main enzymes catalyzing butyrate production: butyrate kinase (Buk) and butyryl-CoA:acetate CoA-transferase (But), which are often used as biomarkers for the detection of butyrate-producing bacteria.11 Buk catalyzes the formation of butyrate from butyryl-CoA, releasing ATP in the process. 12,13 But catalyzes the reaction of butyryl-CoA with exogenous acetate to form butyrate and acetyl-CoA.13,14 Some butyrate-producing bacteria only express But or Buk, whereas others express both. 12The main butyrate producers in the human gut belong to the Firmicutes phylum (Coprococci, Eubacterium, Roseburia, and Faecalibacterium genera), 14 but members of other phyla, especially Bacteroidetes (Odoribacter and Alistipes genera), often contribute to the overall butyrogenic pool. SCFAproducing bacteria may affect blood pressure by direct effects of SCFA on vasodilation or through plasminogen activator inhibitor-1 (PAI-1). n-Butyrate increases PAI-1 mRNA in cultured hepatocytes, 15 and SCFA enemas stimulate rectal microcirculation and PAI-1 after aortic graft surgery. 16 It is uncl...

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“…Reith ve arkadaşları PAI-1 ve PAI-2 üzerine yaptıkları bir çalışmada, preeklampsi olgularında PAI-1'in yükseldiğini ve muhtemelen plasental kitlede veya plasenta fonksiyonlarında azalmaya bağlı olarak PAI-2 düzeyinin belirgin olarak düştüğünü göstermişlerdir. Normal ve anormal gebeliklerin ayrımında PAI-1/PAI-2 oranının kullanılmasının yararlı olacağını öne sürmektedirler [17]. Polikistik over sendromlu kadınlar üzerine çalışmalar yapan Glueck ve arkadaşları PAI aktivitesinin düşük olguları için bağımsız bir risk faktörü olduğunu ileri sürmüşlerdir [18].…”

Section: Introductionunclassified

Plazminojen aktivatör inhibitor-1 (PAI-1) 4g/4g polimorfizminin gebelik kayıplarıyla ilişkisi

Yıldırım¹,

Dağ²,

Kurtulgan³

et al. 2014

Cumhuriyet Med J

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Amaç. Plazminojen aktivatör İnhibitörü Tip 1 (PAI-1) bir serin proteaz inhibitörüdür. Doku plazminojen aktivatörü (tPA) ve ürokinazı (uPA), sonuç olarak fibrinolizi inhibe eder. Genin promotor bölgesinde 4G/5G olarak bilinen bir polimorfizm söz konusudur. Trombozdaki rolü nedeniyle PAI-1 4G/4G polimorfizminin gebelik komplikasyonlarına katkısı olabileceği düşünülmektedir. Biz bu çalışmada, PAI-1 4G/4G polimorfizminin gebelik kayıplarına olası etkisini değerlendirmeyi amaçladık. Yöntem. Çalışma grubu Sivas bölgesinde yaşayan bireylerden seçildi. Araştırmaya 92'si bir veya daha fazla düşük öyküsü olan ve 86 kontrol olmak üzere toplam 178 kadın dahil edildi. Gen mutasyonlarını belirlemek için periferik kan örneklerinden DNA izolasyonu ve sonrasında revers hibridizasyon ilkesine dayanan strip assay tekniği ile mutasyon analizi yapıldı. Veriler SPSS 15,0 istatistik programı aracılığıyla değerlendirildi. Bulgular. Kontrol grubunda 5G/5G polimorfizmi 22 (%25,6), 4G/5G polimorfizmi 53 (%61,6) ve 4G/4G mutant olgular 11 (%12,8) olarak tespit edilmiştir. Düşük olgularında ise 5G/5G polimorfizmi 20 (%21,7), 4G/5G polimorfizmi 49 (53,3) ve 4G/4G mutant olgular ise 23 (%25) bulunmuştur. 4G/4G homozigot mutant olgular için ODDS değeri hesaplanmıştır. Sonuç. Bulgularımıza göre 5G/5G ve 4G/5G polimorfizmleri düşük açısından risk artışı sağlamamaktadır (p=0,546 ve p=0,259 p>0,05). Çalışmamızda PAI-1 4G/4G polimorfizminin düşük riskine katkısı anlamlı bulunmuştur. Bu polimorfizme sahip kadınlarda düşük yapma riski 2,27 kat daha fazladır (p=0,038 p<0,05).Anahtar sözcükler: PAI-1, 4G/4G polimorfizmi, düşük Abstract Aim. Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor. It inhibits tissue plasminogen activator (tPA) and urokinase (uPA), and consequently inhibits fibrinolysis. There is a common polymorphism known as 4G/5G in the promoter region of PAI-1 gene. PAI-1 4G/4G polymorphism may contribute pregnancy complications because of its role in thrombosis,. In this study, we aimed to evaluate the possible effect of PAI-1 4G/4G polymorphism to miscarriages. Method. The study group was selected between individuals residing in Sivas region. One hundred and seventy eight women (92 of them have miscarriage story and 86 control) were incorporated to study. After DNA isolation, mutation analysis was performed by StripAssay technique based on the reverse-hybridization principle. Data were analysed by SPSS 15.0 statistic program. Results. In control group, the number of 5G/5G polymorphisms was 22 (25.6%), the number of 4G/5G polymorphisms was 53 (61.6%) and the number of 4G/4G mutant cases was 11 (12.8%). In miscarriage group, the number of 5G/5G polymorphisms was 20 (21.7%), the number of 4G/5G polymorphisms was 49 (53.3%) and the number of 4G/4G mutant cases was 23 (25%). ODDS ratio was calculated for 4G/4G homozygot mutant cases. Conclusion. According to our datas, 5G/5G and 4G/5G polymorphism have not higher risk for miscarriage (p=0.546 and p=0.259 p>0.05). In our study, it was detected that the contribution ...

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Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole

Cited by 16 publications

References 13 publications

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia

Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy

Plazminojen aktivatör inhibitor-1 (PAI-1) 4g/4g polimorfizminin gebelik kayıplarıyla ilişkisi

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