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 Chaperones. 2008 Summer;13(2):199-206. doi: 10.1007/s12192-007-0001-5. Epub 2008 Feb 22.

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, gammaGT (p < 0.05) concentrations in patients with severe CHF, although no correlation was observed between Hsp70 and CRP, TNF-alpha, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Biomarkers
  • C-Reactive Protein / analysis
  • Cross-Sectional Studies
  • Cytokines / blood
  • Female
  • HSP70 Heat-Shock Proteins / blood*
  • HSP70 Heat-Shock Proteins / genetics
  • Heart Failure / blood*
  • Heart Failure / diagnostic imaging
  • Heart Failure / genetics
  • Humans
  • Inflammation / blood
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index
  • Single-Blind Method
  • Stroke Volume
  • Tumor Necrosis Factor-alpha / analysis
  • Ultrasonography
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / diagnostic imaging

Substances

  • Biomarkers
  • Cytokines
  • HSP70 Heat-Shock Proteins
  • HSPA1B protein, human
  • Inflammation Mediators
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein