Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia

  • Attila Molvarec
  • János RigóJr
  • Levente Lázár
  • Krisztián Balogh
  • Veronika Makó
  • László Cervenak
  • Miklós Mézes
  • Zoltán Prohászka
Original Paper

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.

Keywords

Biomarker Heat-shock protein 70 Hepatocellular injury Inflammation Oxidative stress Preeclampsia 

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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Copyright information

© Cell Stress Society International 2008

Authors and Affiliations

  • Attila Molvarec
    • 1
  • János RigóJr
    • 2
  • Levente Lázár
    • 2
  • Krisztián Balogh
    • 3
  • Veronika Makó
    • 4
  • László Cervenak
    • 5
  • Miklós Mézes
    • 6
  • Zoltán Prohászka
    • 4
    • 5
  1. 1.1st Department of Obstetrics and GynecologySemmelweis UniversityBudapestHungary
  2. 2.1st Department of Obstetrics and GynecologySemmelweis UniversityBudapestHungary
  3. 3.Research Group of Animal Breeding and Hygiene, Faculty of Animal ScienceUniversity of KaposvárKaposvárHungary
  4. 4.3rd Department of Internal Medicine and Szentágothai Knowledge CenterSemmelweis UniversityBudapestHungary
  5. 5.Research Group of Inflammation Biology and ImmunogenomicsHungarian Academy of SciencesBudapestHungary
  6. 6.Department of Nutrition, Faculty of Agricultural and Environmental SciencesSzent István UniversityGödöllőHungary

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