Markers of Endothelial Activation in Preeclampsia

Procházka, Martin; Procházková, Jana; Ľubušký, Marek; Pilka, R; Úlehlová, Jana; Michalec, Igor; Polák, Petr; Kacerovský, Marian; Slavík, Luděk

doi:10.7754/clin.lab.2014.140521

Cited by 18 publications

(20 citation statements)

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“…For Instance, THBD , an endothelial cell-specific membrane-bound receptor that functions as an anticoagulant, was highly up-regulated by HtrA4. This is consistent with other studies showing that serum THBD is increased in PE women compared to normal controls [39], [40], and that THBD is a potential marker of endothelial dysfunction to predict PE [39]. Furthermore, increased levels of THBD in the maternal circulation negatively correlate to infant birth weight, and the highest plasma THBD level was detected in PE pregnancy with intrauterine growth restriction, which is often associated with early-onset PE.…”

Section: Discussionsupporting

confidence: 91%

High levels of HtrA4 observed in preeclamptic circulation drastically alter endothelial gene expression and induce inflammation in human umbilical vein endothelial cells

Wang

Nie

2016

Placenta

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IntroductionPreeclampsia (PE) is a life-threatening pregnancy disorder characterized by wide-spread endothelial dysfunction. Placental factors circulating in the maternal blood are believed to cause endothelial dysfunction. Our previous study identified HtrA4 as a placenta-specific serine protease that is released into the maternal circulation and significantly increased in early-onset PE. In this study, we examined the impact of HtrA4 on expression of endothelial genes related to vessel biology, using human umbilical vein endothelial cells (HUVECs) as a model.MethodsHUVECs were treated with 0 or 3 μg/ml HtrA4 (highest concentration seen in PE circulation) for 24 h and analysed by an endothelial cell biology PCR array containing 84 genes. HtrA4-induced changes were then validated by real-time RT-PCR and ELISA for time and dose dependency.ResultsHigh levels of HtrA4 significantly altered the expression of a range of genes related to inflammation, vaso-activity, angiogenesis, cell adhesion, platelet activation and coagulation. In particular, pro-inflammatory genes IL6, PTGS2 (COX2) and IL1B were significantly increased by HtrA4. IL6 protein in HUVEC media was also drastically increased. THBD, an anticoagulant factor reported to be increased in PE, was significantly up-regulated by HtrA4. In contrast, THBS1, which is involved in many regulatory processes of endothelial cell biology, was severely down-regulated by HtrA4.DiscussionHtrA4 significantly increased the inflammatory responses of HUVECs, and altered their expression of a number of genes important for vessel biology. These data suggest that placenta-derived HtrA4 that is increased in PE circulation is a potential causal factor of endothelial dysfunction.

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Section: Discussionsupporting

confidence: 91%

High levels of HtrA4 observed in preeclamptic circulation drastically alter endothelial gene expression and induce inflammation in human umbilical vein endothelial cells

Wang

Nie

2016

Placenta

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“…It was established that in all women with hypertensive disorders irrespective of their genesis DE and NOx levels were statistically significantly higher ( DE are known to be specific markers of damage to inner vessel bed. Increased DE content in the blood of pregnant women with hypertensive disorders reflects the very process of endotheliosis induced by the influence of endotoxins, superoxide radicals, homocysteine, histamine and other damaging factors [19]. Our findings are consistent with the studies revealing the fact that the level of circulating endotheliocytes increases in pregnant women with hypertensive disorders [20].…”

supporting

confidence: 91%

Markers of Endothelial Dysfunction as Criteria for Differential Diagnosis of Hypertensive Disorders in Pregnant Women

Rokotyanskaya¹,

Малышкина²,

Назаров³

et al. 2016

Sovrem Tehnol Med

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The aim of the investigation was to study indicators of microvasculature oxygenation and markers of endothelial dysfunction in the peripheral blood of pregnant women with various hypertensive disorders and on the basis of the resulting findings to suggest new diagnostic criteria for this pathology.Materials and Methods. The study involved 153 women at 22-37 weeks gestation: 41 women with chronic arterial hypertension (CAH), 22 women with CAH and secondary preeclampsia (PE), 50 women with PE, 40 women with normal blood pressure. The level of tissue oxygenation (SO 2 ) was estimated by test with ischemia/reperfusion (Spectrotest, Russia). Desquamated endotheliocytes (DE), total nitrates and nitrites (NOx) were determined in the peripheral blood.Results. All kinds of hypertensive disorders in pregnant women are accompanied by the development of endothelial dysfunction as evidenced by the change in the level of tissue oxygenation, increase in DE and NOx content in the blood. The extent of endothelial function impairment depends on PE severity.Conclusion. Changes in endothelium-dependent vascular response found as the result of test with ischemia/reperfusion and the content of venous endothelial cells in pregnant women with hypertensive disorders may serve as diagnostic criteria of hypertensive disorders in pregnancy, giving the possibility to choose tactics of patient management and to start well-timed adequate therapy.

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“…44,45 In early pregnancy, increased PAI-1 levels are associated with higher risk of later hypertensive disorders in pregnancy. 46 PAI-1 levels are also increased in severe preeclampsia, 23 and polymorphisms in the PAI-1 gene (SERPINE2) have been associated with increased risk of preeclampsia in a meta-analysis. 47 It is not clear whether PAI-1 regulates blood pressure or vice versa; however, one study suggests that inhibition of PAI-1 can reduce hypertension caused by inhibition of nitric oxide synthase.…”

Section: Gomez-arango Et Al Blood Pressure and Gut Microbiome Butyratmentioning

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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Markers of Endothelial Activation in Preeclampsia

Cited by 18 publications

References 0 publications

High levels of HtrA4 observed in preeclamptic circulation drastically alter endothelial gene expression and induce inflammation in human umbilical vein endothelial cells

High levels of HtrA4 observed in preeclamptic circulation drastically alter endothelial gene expression and induce inflammation in human umbilical vein endothelial cells

Markers of Endothelial Dysfunction as Criteria for Differential Diagnosis of Hypertensive Disorders in Pregnant Women

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

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