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Interaction of serum 70-kDa heat shock protein levels and HspA1B (+1267) gene polymorphism with disease severity in patients with chronic heart failure

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Cell Stress and Chaperones Aims and scope

Abstract

Background

Circulating heat shock protein 70 (Hsp70) is present in the circulation of healthy individuals and in patients with various disorders, including chronic heart failure (CHF). However, the source and routes of release of Hsp70 is only partially characterised in clinical samples.

Aims

The purpose of this study was to study the clinical and biological correlates of Hsp70 in a CHF population and, for the first time, to investigate the association of HspA1B (also known as Hsp70-2) +1267 alleles with serum Hsp70 levels.

Methods

A total of 167 patients (123 men, 44 women) with <45% left ventricular ejection fraction (LVEF) were enrolled; serum Hsp70 level was determined by enzyme-linked immunosorbent assay and HspA1B +1267 polymorphism by polymerase chain reaction–restriction fragment length polymorphism.

Results

Increased Hsp70 levels were present in patients with severe CHF (NYHA III–IV) as compared to the group of NYHA I–II (p = 0.003). Hsp70 levels correlated with LVEF, NT-proBNP, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, γGT (p < 0.05) concentrations in patients with severe CHF, although no correlation was observed between Hsp70 and CRP, TNF-α, or IL-6. HspA1B allele G was associated with higher Hsp70 levels (p = 0.001) in patients in NYHA IV class as compared to carriers of allele A.

Conclusions

Serum Hsp70 levels were associated with disease severity in heart failure patients. An interaction with the presence of HspA1B +1267 allele G was observed for Hsp70 concentrations. Hsp70 correlates with markers of heart function and hepatic injury, but not with signs of inflammation.

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Abbreviations

CHF:

chronic heart failure

Hsp:

heat shock protein

AMI:

acute myocardial infarction

HELLP syndrome:

haemolytic anemia elevated liver enzymes low platelet count

TNF:

tumour necrosis factor

Il-6:

interleukin-6

EF:

ejection fraction

BMI:

body mass index

NT-proBNP:

N-terminal pro-brain natriuretic peptide

NYHA:

New York Heart Association

AST:

aspartate aminotransferase

ALT:

alanine aminotransferase

γGT:

gamma-glutamyl transpeptidase

CRP:

C-reactive protein

RBC:

red blood cell count

NIDDM:

non-insulin-dependent diabetes mellitus

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Acknowledgements

This work was supported by the following grants: Hungarian Scientific Research Fund (OTKA T046837) and Ministry of Health (ETT 229/2006). The skilful technical assistance of Szigeti Antalné, Margit Kovács, Holeczky Rudolfné and Piroska Sturmann and the helpful suggestions of Katalin Udvarnoki regarding the sHsp70 assay are acknowledged with many thanks.

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Correspondence to Zoltán Prohászka.

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Gombos, T., Förhécz, Z., Pozsonyi, Z. et al. Interaction of serum 70-kDa heat shock protein levels and HspA1B (+1267) gene polymorphism with disease severity in patients with chronic heart failure. Cell Stress and Chaperones 13, 199–206 (2008). https://doi.org/10.1007/s12192-007-0001-5

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  • DOI: https://doi.org/10.1007/s12192-007-0001-5

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