Correlation Between Maternal Plasma Thrombomodulin and Infant Birth Weight in Hypertensive Disorders of Pregnancy

Varol, Füsun; Özgen, Levent; Sayın, N. Cenk; Demir, Muzaffer

doi:10.1177/1076029608325543

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…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. It was suggested that the damage to endothelium as a result of THBD dysregulation could have a major impact on fetal development [41].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…In pregnancy, fibrinolysis is controlled by the maternal endothelium and placenta, both of which are central to the pathogenesis of some obstetric pathologies [14]. Some works have discussed that plasma Thrombomodulin levels might point out placental vascular endothelial damage reflecting on birthweight [15]. On the contrary, other studies have focused the attention on the role of the Thrombomodulin in cell invasivity and capability to perform intravasation and extravasation, during local invasion.…”

Section: Discussionmentioning

confidence: 99%

Placental thrombomodulin expression in recurrent miscarriage

Stortoni

Cecati

Giannubilo

et al. 2010

Reprod Biol Endocrinol

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BackgroundEarly pregnancy loss can be associated with trophoblast insufficiency and coagulation defects. Thrombomodulin is an endothelial-associated anticoagulant protein involved in the control of hemostasis and inflammation at the vascular beds and it's also a cofactor of the protein C anticoagulant pathway.DiscussionWe evaluate the Thrombomodulin expression in placental tissue from spontaneous recurrent miscarriage and voluntary abortion as controls. Thrombomodulin mRNA was determined using real-time quantitative polymerase chain reaction. Reduced expression levels of thrombomodulin were found in recurrent miscarriage group compared to controls (1.82-fold of reduction), that corresponds to a reduction of 45% (from control group Delta CT) of thrombomodulin expression in spontaneous miscarriage group respect the control groups.SummaryWe cannot state at present the exact meaning of a reduced expression of Thrombomodulin in placental tissue. Further studies are needed to elucidate the biological pathway of this important factor in the physiopathology of the trophoblast and in reproductive biology.

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“…During pregnancy, TM prevents the uteroplacental circulation from thrombotic events [ 47 ]. In pregnant women with hypertensive disorders of pregnancy, elevated plasma TM levels correlate with low birth weight [ 48 ]. The authors outlining the above findings speculate that elevated plasma TM levels might protect against the endothelial alterations of these conditions.…”

Section: Discussionmentioning

confidence: 99%

Early Mid-pregnancy Blood-Based Proteins as Possible Biomarkers of Increased Infant Birth Size in Sex-Stratified Analyses

et al. 2022

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The objective of this study was to evaluate the associations of 92 maternal blood-based proteins with increased infant birth size. The study was performed at the Uppsala University Hospital, Sweden, and included 857 mother and child dyads. The mean age of the women was 30.3 years, and 53.2% were nulliparous. Blood samples were collected at mean 18 + 2 weeks’ gestation, and the Olink cardiovascular II panel was used to measure 92 proteins, either known to be or suspected to be markers of cardiovascular and inflammatory disease in humans. Multiple linear regression models adjusted for maternal age, parity, pre-conception BMI, height, and smoking were performed to evaluate the association of each individual protein with infant birth size. We also performed sex-stratified analyses. Eight proteins (Matrix metalloproteinase-12 (MMP-12), Prostasin (PRSS8), Adrenomedullin (ADM), Pappalysin-1 (PAPP-A), Angiotensin-converting enzyme 2 (ACE2), Sortilin (SORT1), Lectin-like oxidized LDL receptor 1 (LOX-1), and Thrombomodulin (TM)) were associated with infant birth size after false discovery rate adjustment. In the analyses including only female infants, ten proteins (MMP-12, Growth/differentiation factor 2 (GDF-2), PRSS8, SORT1, ADM, Interleukin-1 receptor antagonist protein (IL-1ra), Leptin (LEP), ACE2, TM, and Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A)) were associated with infant birth size. Two proteins (PAPP-A and PRSS8) were associated with infant birth size among male infants. Our study suggests several proteins as potential biomarkers for increased birth weight, and our findings could act as a base for future research to identify new potential markers that could be added to improve screening for large infants.

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Correlation Between Maternal Plasma Thrombomodulin and Infant Birth Weight in Hypertensive Disorders of Pregnancy

Abstract: Elevated plasma thrombomodulin levels in hypertensive disorders of pregnancy were well correlated with related infant birth weights of these pathologies. Plasma thrombomodulin levels might point out placental vascular endothelial damage reflecting on infant birth weights.

Cited by 6 publications

References 15 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

Placental thrombomodulin expression in recurrent miscarriage

Early Mid-pregnancy Blood-Based Proteins as Possible Biomarkers of Increased Infant Birth Size in Sex-Stratified Analyses

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