Alpha-1-Antitrypsin Acts as a Preeclampsia-Related Protein: A Proteomic Study

Abstract

Aims: To screen the preeclampsia-related protein by proteomics. Methods: Proteomics was performed to identify differential protein expression profiles between normal full-term pregnancy, early-onset severe preeclampsia (ES-PE) or late-onset severe preeclampsia (LS-PE; n = 10 per group). Real-time quantitative PCR and immunohistochemistry were conducted to confirm the expression of α₁-antitrypsin (α₁-AT) in the decidual tissues of different subjects. ELISA was employed to detect the α₁-AT content in the peripheral blood of 90 women (n = 30 per group). Results: We successfully constructed two-dimensional electrophoresis maps of decidual tissues, and a total of 20 differentially expressed proteins were identified. The α₁-AT expression was different among the three groups. The normal full-term pregnancy women expressed the most α₁-AT, and the LS-PE women expressed the least amount of α₁-AT. The difference in the α₁-AT expression was consistent with the proteomics data. The peripheral α₁-AT content was the highest in the normal full-term pregnancy group (1.85 ± 0.15 g/l), moderate in the ES-PE group (0.77 ± 0.14 g/l) and lowest in the LS-PE group (0.42 ± 0.07 g/l; p < 0.05). Conclusion: Using 2D PAGE, we identified twenty proteins with significantly altered expression in PE. These differentially expressed proteins include prevention protein, in which α₁-AT is downregulated in PE.

The human placental proteome is affected by maternal smoking

“…According to the literature there are contradictory data based on placental SERPINA1 protein expression levels. This is due to the differences in risk factors for pregnancy: SERPINA1 was increased in placentas of obese mothers [26] and decreased in preeclamptic mothers [27]. SERPINA1 is increased in the lung and sputum of smokers [28], which, together with our data and known effects of smoking on the placenta [29], suggests that specific SERPINA1 isoforms could serve as a biomarker for oxidative stress.…”

“…Lower levels of proteins associated with haemoglobin synthesis could lead to inadequate oxygen transfer to the foetus and increase risk of intrauterine oxygen depletion and foetal growth retardation seen in maternal smoking. Similarly, placentae from severe preeclamptic mothers have demonstrated comparable decrease in haemoglobin–β-chain levels [27]. In contrast, HBB, HBA and HBG levels were significantly elevated in proteomic studies of: (i) cord blood from maternal smokers [33] and (ii) the effects of growth restriction on the human placenta [30].…”

Beyond thelungs: Alpha-1 antitrypsin’s potential role in human gestation

“…14 Furthermore, AAT may play a role in fertility regulation, pregnancy loss and other obstetric pathologies. [15][16][17][18][19][20][21][22] Finally, there is data from maternal serum protein profiling showing that alpha-1-antitrypsin is among the markers for non-invasive prenatal diagnoses of trisomy 21, 18 and 13. 23…”

“…22 This is in line with other reports of significantly increased AAT levels in patients with clinical symptoms of severe PE vs those with uncomplicated pregnancies. 19,29,30 Obviously, this might simply result from inflammatory components of pregnancies complicated by EOPE, but AAT should also be considered a candidate biomarker or part of a biomarker panel in early screening for EOPE.…”

Mechanisms of anti-infective fetal protection

“…Данный белок, как и α 2 -МГ, является ингибитором протеиназ, синтезируется преимущественно в печени, но также моноцитами, эпителиальными клетками, тканями трофобласта [45]. Концентрации α 1 -антитрипсина повышаются при беременности [46], а его дефицит ассоциирован с такими осложнениями беременности, как преждевременные роды [47] и преэклампсия [48]. С другой стороны, показано повышение экспрессии α 1 -антитрипсина амниотическими эпителиальными клетками после стимуляции IL-6 или TNF-α, что, как полагают, и происходит при хориоамнионите.…”