TY - JOUR
T1 - Activation of the NF-κB system in peripheral blood leukocytes from patients with chronic heart failure
AU - Jankowska, Ewa A.
AU - Von Haehling, Stephan
AU - Czarny, Anna
AU - Zaczynska, Ewa
AU - Kus, Agnieszka
AU - Anker, Stefan D.
AU - Banasiak, Waldemar
AU - Ponikowski, Piotr
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
KW - Chronic heart failure
KW - Immune activation
KW - Nuclear factor kappa-B
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U2 - 10.1016/j.ejheart.2005.05.013
DO - 10.1016/j.ejheart.2005.05.013
M3 - Article
C2 - 16112903
AN - SCOPUS:26644469057
VL - 7
SP - 984
EP - 990
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
SN - 1388-9842
IS - 6
ER -