Abstract

BackgroundPreeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties that has been much studied in various animal models of inflammation but poorly studied in the context of human inflammatory diseases. The main objective of this study was to measure AnxA1 levels in PE women and to compare those levels in normotensive pregnant and non-pregnant women. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants.MethodsThis study included 40 non-pregnant, 38 normotensive pregnant and 51 PE women. PE women were stratified in early (N = 23) and late (N = 28) subgroups, according to gestational age (GA) at onset of clinical symptoms. Protein AnxA1 and us-CRP plasma levels were determined by ELISA and immunoturbidimetric assays, respectively. Transcript levels of AnxA1 in peripheral blood mononuclear cells (PBMC) were measured by real time RT-PCR.ResultsIncreased levels of AnxA1 coincided with higher us-CRP levels in the plasma of PE women. Pregnant women with early PE had higher levels of AnxA1 and us-CRP than normotensive pregnant women with GA <34 weeks. No significant difference was found for AnxA1 and us-CRP, comparing late PE and normotensive pregnant women with GA ≥34 weeks. AnxA1 mRNA levels in PBMC were similar among the studied groups. AnxA1 was positively correlated with sTNF-R1, but not with us-CRP.ConclusionsOur data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis. However, more studies are needed to clarify the role of AnxA1 and other proresolving molecules in the context of the systemic inflammatory response in this intriguing disease.

Highlights

  • Preeclampsia (PE) is a multisystem disease characterized by new-onset hypertension and proteinuria on or after 20 weeks of gestation [1]

  • Increased levels of Annexin A1 (AnxA1) coincided with higher ultrasensitive C reactive protein (us-C-reactive protein (CRP)) levels in the plasma of PE women

  • Our data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis

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Summary

Introduction

Preeclampsia (PE) is a multisystem disease characterized by new-onset hypertension and proteinuria on or after 20 weeks of gestation [1]. It has been proposed that the ischemic placenta can release soluble factors into the maternal circulation that cause endothelial cell activation and/or dysfunction and a systemic inflammatory response [4]. Redman et al initially proposed that the features of the systemic inflammatory response observed in normotensive pregnant women are seen in PE women, but in a greater intensity [5]. Several studies have described increased activation of circulating leukocytes, abnormal immune cell phenotype and higher pro-inflammatory markers levels, such as C-reactive protein (CRP), in PE compared to normotensive pregnancy [6,7,8,9,10]. Preeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants

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