Abstract
It has been previously reported that serum levels of 70-kDa heat-shock protein (Hsp70) are elevated in preeclampsia. The aim of the present study was to examine whether increased serum Hsp70 levels are related to clinical characteristics and standard laboratory parameters of preeclamptic patients, as well as to markers of inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) or endothelial injury (fibronectin), trophoblast debris (cell-free fetal DNA) and oxidative stress (malondialdehyde). Sixty-seven preeclamptic patients and 70 normotensive, healthy pregnant women were involved in this case-control study. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Standard laboratory parameters (clinical chemistry) and C-reactive protein (CRP) levels were determined by an autoanalyzer using the manufacturer’s kits. Plasma von Willebrand factor antigen (VWF:Ag) levels were quantified by ELISA, and plasma fibronectin concentration by nephelometry. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time polymerase chain reaction analysis of the sex-determining region Y gene. Plasma malondialdehyde levels were measured by the thiobarbituric acid-based colorimetric assay. Serum Hsp70 levels were increased in preeclampsia. Furthermore, serum levels of blood urea nitrogen, creatinine, bilirubin and CRP, serum alanine aminotransferase and lactate dehydrogenase (LDH) activities, as well as plasma levels of VWF:Ag, fibronectin, cell-free fetal DNA and malondialdehyde were also significantly higher in preeclamptic patients than in normotensive, healthy pregnant women. In preeclamptic patients, serum Hsp70 levels showed significant correlations with serum CRP levels (Spearman R = 0.32, p = 0.010), serum aspartate aminotransferase (R = 0.32, p = 0.008) and LDH activities (R = 0.50, p < 0.001), as well as with plasma malondialdehyde levels (R = 0.25, p = 0.043). However, there was no other relationship between serum Hsp70 levels and clinical characteristics (age, parity, body mass index, blood pressure, gestational age, fetal birth weight) and laboratory parameters of preeclamptic patients, including markers of endothelial activation or injury and trophoblast debris. In conclusion, increased serum Hsp70 levels seem to reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Nevertheless, further studies are required to determine whether circulating Hsp70 plays a causative role in the pathogenesis of the disease.
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Abbreviations
- ALT:
-
alanine aminotransferase
- ANCOVA:
-
analysis of covariance
- AST:
-
aspartate aminotransferase
- BMI:
-
body mass index
- BUN:
-
blood urea nitrogen
- CD:
-
cluster of differentiation
- CRP:
-
C-reactive protein
- DNA:
-
deoxyribonucleic acid
- EDTA:
-
ethylenediaminetetraacetic acid
- ELISA:
-
enzyme-linked immunosorbent assay
- HELLP:
-
hemolysis, elevated liver enzymes, and low platelet count
- HRP:
-
horseradish-peroxidase
- Hsp:
-
heat-shock protein
- IL:
-
interleukin
- LDH:
-
lactate dehydrogenase
- LOX-1:
-
lectin-like oxidised low-density lipoprotein receptor-1
- MDA:
-
malondialdehyde
- OPD:
-
o-phenylene-diamine
- PBS:
-
phosphate-buffered saline
- PCR:
-
polymerase chain reaction
- RNA:
-
ribonucleic acid
- SRY:
-
sex-determining region Y
- Th1:
-
T helper 1
- TNF-α:
-
tumor necrosis factor-α
- U:
-
unit
- VWF:Ag:
-
von Willebrand factor antigen
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Acknowledgements
The skilful technical assistance of Szigeti Antalné and the support of Szilvia Walentin, Éva Imreh and Mónika Kleiber (Central Laboratory, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary) are acknowledged with many thanks. This work was supported by research grants from the Hungarian Scientific Research Fund (NF 72689) and the Faculty of Medicine of the Semmelweis University.
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Molvarec, A., Rigó, J., Lázár, L. et al. Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Cell Stress and Chaperones 14, 151–159 (2009). https://doi.org/10.1007/s12192-008-0067-8
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DOI: https://doi.org/10.1007/s12192-008-0067-8