Activation of the NF-κB system in peripheral blood leukocytes from patients with chronic heart failure

Ewa A. Jankowska, Stephan Von Haehling, Anna Czarny, Ewa Zaczynska, Agnieszka Kus, Stefan D. Anker, Waldemar Banasiak, Piotr Ponikowski

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To evaluate the activation of transcriptional nuclear factor kappa-B (NF-κB) in peripheral blood leukocytes (PBL) from patients with chronic heart failure (CHF). In vitro experiments were used to elucidate the role of lipopolysaccharide (LPS) as a stimulus for the NF-κB system in PBL. Methods and results: We examined 46 CHF patients (age: 62 ± 1 years, LVEF: 31 ± 1%, NYHA class: 2.7 ± 0.1), 11 coronary artery disease (CAD) patients without CHF, and 13 healthy young subjects. The immunocytochemical localisation of NF-κB in PBL was assessed using a polyclonal rabbit IgG anti-c-Rel-subunit antibody. NF-κB activation was expressed as the percentage of PBL nuclei stained positively for c-Rel (NF-κB(+)cell). PBL from healthy controls were exposed in vitro to the following concentrations of LPS from Escherichia coli (strain O111:B4): 0.1, 10 and 5000 ng/mL. CHF patients demonstrated the highest NF-κB activation in PBL (NF-κB(+)cells [%]: 37.1 ± 1.5) as compared to CAD patients (29.1 ± 3.0%) and controls (12.6 ± 1.5%) (all p <0.05). There were three main clinical determinants of NF-κB activation in PBL from CHF patients: peak oxygen consumption (r = 0.53, p = 0.025), presence of peripheral oedema (r = 0.37, p <0.05) and serum C-reactive protein (r = 0.40, p = 0.02). In PBL from healthy subjects, LPS at all concentrations increased NF-κB activity towards the pattern detected in CHF. Conclusions: The NF-κB system is highly overactive in PBL from CHF patients. LPS at low concentrations in peripheral blood may be involved in NF-κB activation in PBL, and is a potential target for future therapeutic applications.

Original languageEnglish
Pages (from-to)984-990
Number of pages7
JournalEuropean Journal of Heart Failure
Volume7
Issue number6
DOIs
Publication statusPublished - Oct 2005

Keywords

  • Chronic heart failure
  • Immune activation
  • Nuclear factor kappa-B

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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