The role of plasminogen activator inhibitor-1 in gynecological and obstetrical diseases: An update review

Zhang, Jiaqi; Li, Zijian; Zhou, Yue; Yang, Xiuhua

doi:10.1016/j.jri.2022.103490

Cited by 26 publications

(28 citation statements)

References 242 publications

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“…We strongly suggested that these are among the trigger factors of unfavorable pregnancy outcomes in the EPL2 group. Recently it has been reported that the overexpression of PAI-1 is an important indicator of pregnancy complications, including miscarriage [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Altered Thermal Behavior of Blood Plasma Proteome Related to Inflammatory Cytokines in Early Pregnancy Loss

Komsa-Penkova

Danailova

Krumova

et al. 2022

IJMS

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Early pregnancy loss (EPL) is a relatively common pathology of which almost 50% of cases remain idiopathic. In the search for novel biomarkers, differential scanning calorimetry (DSC) is intensively used to characterize the thermodynamic behavior of blood plasma/serum proteome in health and disease. Herein, for the first time, we investigate the DSC denaturation profiles of blood plasma derived from patients suffering EPL compared to healthy pregnant and non-pregnant women. Data analysis reveals that 58% of the EPL thermograms differ significantly from those of healthy pregnant women. Thermal stabilization of a fraction of albumin-assigned transition with concomitant suppression of the major and enhancement of the globulin-assigned transition are characteristic features of EPL calorimetric profiles that could be used as a new indicator of a risk pregnancy. The presented results suggest an altered composition or intermolecular interactions of the plasma proteome of women with EPL. In addition, the alterations of the EPL thermograms correlate with the increased blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and a higher prevalence of the polymorphism in the plasminogen activator inhibitor type-1 (PAI-1) gene, suggesting an expression of an overall enhanced immune response. The concomitant changes in plasma thermograms confirm the potential of the DSC approach for distinguishing changes in the pathological state of the blood plasma proteome.

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Section: Discussionmentioning

confidence: 99%

Altered Thermal Behavior of Blood Plasma Proteome Related to Inflammatory Cytokines in Early Pregnancy Loss

Komsa-Penkova

Danailova

Krumova

et al. 2022

IJMS

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“…It has been reported that the hypoinvasion and failed conversion of maternal endometrial spiral arteries in the placenta of patients with PET are related to the increased level of PAI-1 ( Redman and Sargent, 2005 ). Additionally, PET has been commonly recognized as an inflammation-mediated disorder, and inflammatory cytokines, including interleukin 1β (IL-1β), IL-6, vascular endothelial growth factor, and epidermal growth factor, could upregulate the level of circulating PAI-1 ( Zhai et al, 2022 ). Moreover, it has been found that the NF-κB pathway activation in the damaged migration of trophoblasts in PET could ultimately promote the mRNA expression of PAI-1 ( Ye et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study

et al. 2022

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Background: Several observational studies have demonstrated that significantly rising circulating adipokine levels are pervasive in preeclampsia or eclampsia disorder (or preeclampsia toxemia (PET)). However, it remains unclear whether this relationship is causal. In this study, we sought to elucidate the causal effects of circulating adipokine levels on PET.Methods: Summary-level data and independent genetic variants strongly associated with common adipokine molecule (adiponectin, leptin, resistin, sOB-R, and PAI-1) levels were drawn from public genome-wide association study (GWASs). Additionally, the corresponding effects between instrumental variables and PET outcomes were acquired from the FinnGen consortium, including 4,743 cases and 136,325 controls of European ancestry. Subsequently, an inverse-variance weighted (IVW) approach was applied for the principal two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Various complementary sensitivity analyses were then carried out to determine the robustness of our models.Results: The results of the IVW method did not reveal any causal relationship shared across genetically predisposed adipokine levels and PET risk (for adiponectin, OR = 0.86, 95% CI: 0.65–1.13, p = 0.274). Additionally, no significant associations were identified after taking into account five circulating adipokines in MVMR research. Complementary sensitivity analysis also supported no significant associations between them. In the reverse MR analysis, genetically predicted PET risk showed a suggestive association with elevating PAI-1 levels by the IVW method (Beta = 0.120, 95% CI: 0.014, 0.227, p = 0.026). Furthermore, there were no strong correlations between genetic liability to PET and other adipokine levels (p > 0.05).Conclusion: Our MR study did not provide robust evidence supporting the causal role of common circulating adipokine levels in PET, whereas genetically predicted PET may instrumentally affect PAI-1 levels. These findings suggest that PAI-1 may be a useful biomarker for monitoring the diagnosis or therapy of PET rather than a therapeutic target for PET.

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“…It has been reported that GDM was resolved in 90% of cases after delivery [ 10 ]. Though, pregnant women with GDM are at high risk for the development of type 2 DM (T2DM), preeclampsia and depression [ 8 , 11 , 12 ]. Neonates from mothers with GDM may develop hypoglycemia, severe jaundice, and large body weight [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Plasminogen activator inhibitor 1 and gestational diabetes: the causal relationship

Batiha

Al-Kuraishy

Al-Maiahy

et al. 2022

Diabetol Metab Syndr

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Plasminogen activator inhibitor 1 (PAI-1) also known as serpin E1 or endothelial plasminogen activator inhibitor, is produced from endothelial cells and adipose tissue. PAI-1 inhibits tissue plasminogen activator (tPA) and urokinase (uPA) preventing activation of plasminogen and fibrinolysis. Gestational diabetes mellitus (GDM) is defined as glucose intolerance and hyperglycemia during pregnancy. The underlying mechanism of GDM is due to the reduction of insulin secretion or the development of insulin resistance (IR). Normal PAI-1 is a crucial mediator for maintaining pregnancy, though aberrantly high PAI-1 promotes inflammation and thrombosis with increased risk of pregnancy loss. Increasing PAI-1 level had been shown to be an early feature of cardio-metabolic derangement in women with GDM. As well, GDM is regarded as an independent predictor for increasing PAI-1 levels compared to normal pregnancy. Taken together, GDM seems to be the causal factor in the increase of PAI-1 via induction of IR, hyperglycemia and hypertriglyceridemia. In conclusion, GDM triggers expression and release of PAI-1 which linked with GDM severity due to exaggerated pro-inflammatory and inflammatory cytokines with the development of IR. High PAI-1 levels in GDM may induce hypofibrinolysis and thrombotic complications.

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The role of plasminogen activator inhibitor-1 in gynecological and obstetrical diseases: An update review

Cited by 26 publications

References 242 publications

Altered Thermal Behavior of Blood Plasma Proteome Related to Inflammatory Cytokines in Early Pregnancy Loss

Altered Thermal Behavior of Blood Plasma Proteome Related to Inflammatory Cytokines in Early Pregnancy Loss

Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study

Plasminogen activator inhibitor 1 and gestational diabetes: the causal relationship

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