Circulating heat shock protein mRNA profile in gestational hypertension, pre-eclampsia & foetal growth restriction
Ilona Hromadnikova1, Lenka Dvorakova1, Katerina Kotlabova1, Andrea Kestlerova2, Lucie Hympanova3, Veronika Novotna2, Jindrich Doucha4, Ladislav Krofta2
1 Department of Molecular Biology & Cell Pathology, The Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic
2 The Third Faculty of Medicine, Institute for the Care of the Mother & Child, Charles University, Podolske Nabrezi 157/36, 147 00 Prague, Czech Republic
3 Department of Molecular Biology & Cell Pathology, The Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague; The Third Faculty of Medicine, Institute for the Care of the Mother & Child, Charles University, Podolske Nabrezi 157/36, 147 00 Prague, Czech Republic
4 Clinic of Obstetrics & Gynecology, The Second Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
Department of Molecular Biology & Cell Pathology, The Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague 10
Source of Support: None, Conflict of Interest: None
Background & objectives: Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction.
Methods: Pregnancies with gestational hypertension (GH) (n = 33), pre-eclampsia (PE) with or without foetal growth restriction (FGR) (n = 78) and FGR (n = 25) were involved in the study. Hsp gene expression was analysed in relation to the severity of the disease with respect to the degree of clinical signs, requirements for the delivery and Doppler ultrasound parameters.
Results: Upregulation of Hsp70 was observed in patients with mild and severe PE (P = 0.004 and P = 0.005, respectively) and in pregnancies complicated with PE delivering before and after 34 wk of gestation regardless of the degree of clinical signs (P = 0.015 and P = 0.009, respectively). No difference in the expression of other Hsp genes among the studied groups was observed. No association between Hsp gene expression and Doppler ultrasonography parameters was found.
Interpretation & conclusions: These data support that maternal circulation can reflect both maternal and foetal pathologic conditions. Hsp70 represents the sole plasmatic marker, and increased Hsp70 mRNA levels reflect maternal and placental stress response to pregnancy-related complications such as GH and PE, irrespective of the severity of the disease.