Annexin A1 Is Increased in the Plasma of Preeclamptic Women

<div><p>Background</p><p>Preeclampsia (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.</p><p>Methods</p><p>This 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.</p><p>Results</p><p>Increased 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.</p><p>Conclusions</p><p>Our 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.</p></div

AnxA1 mRNA expression in PBMC of non-pregnant, normotensive pregnant and PE women.

<p>NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women). Horizontal bars represent median values for Anx1 mRNA fold change expression relative to the calibrator group (Norm). The transcript levels of AnxA1 were similar among the study groups.</p

us-CRP plasma levels in normotensive pregnant and PE women according to gestational age.

<p>Norm<34 wks (normotensive pregnant women with GA<34 weeks), Norm≥34 wks (normotensive pregnant women with GA≥34 weeks), PE (preeclamptic women). Horizontal bars represent median us-CRP levels (milligrams/liter). *P<0.05. Plasma levels of us-CRP were higher in normotensive pregnant women (GA≥34 weeks) than in normotensive pregnant women (GA<34 weeks) (A). Pregnant women with early PE had higher levels of us-CRP than normotensive pregnant women with GA<34 weeks (C). No significant differences were found between pregnant women with early and late PE (B) and between pregnant women with late PE and normotensive pregnant women GA≥34 weeks (D).</p

AnxA1 plasma levels in non-pregnant, normotensive pregnant and PE women.

<p>NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women). Horizontal bars represent median values for AnxA1 (micrograms/milliliter). **P<0.01, *P<0.05. Plasma levels of AnxA1 were higher in PE women than in normotensive pregnant and non-pregnant women. No significant differences were found comparing non-pregnant and normotensive pregnant women.</p

us-CRP plasma levels in non-pregnant, normotensive pregnant and PE women.

<p>NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women). Horizontal bars represent median values for us-CRP (milligrams/liter). ***P<0.001. Plasma levels of us-CRP were higher in normotensive pregnant women compared to non-pregnant women and in PE women than in non-pregnant women. No significant difference was detected between PE and normotensive pregnant women.</p