Elevated circulating levels of thioredoxin and stress in chronic heart failure

Chronic heart failure (CHF) is a complex syndrome, in which reactive oxygen species and inflammatory cytokines are important stressors that contribute to the pathogenesis. Aim: We have studied physiological stress response parameters in CHF, in particular the redox-active regulator thioredoxin. Subjects: A case-control study was conducted including a consecutive sample of CHF patients (n = 27) of NYHA class II and III; comparison control subjects (n = 29) were recruited from an association for retired people. Method: Baseline levels of Trx, lipid peroxides (oxidative stress), TNF and IL-6 cytokines, platelet-activation marker P-selectin, cortisol (as peripheral effector of HPA axis), and the potent antioxidant selenoprotein Trx-reductase were assessed. Results: Mean ( +/- S.E.M.) plasma levels of Trx were significantly higher in patients with CHF (32 +/- 3 ng/ml), than in the healthy subjects (12 +/- 3 ng/ml, P < 0.0001). Trx levels increased in proportion to severity of disease (NYHA class III > NYHA class II) and degree of stress. Trx elevation correlated well with increased oxidative stress (lipid peroxides, P < 0.0001), circulatory P-selectin (P < 0.0001), morning level of free salivary cortisol (P = 0.0002), and serum creatinine (P = 0.0417), but not with pro-inflammatory cytokines TNF and IL-6. Conclusion: Trx was strikingly elevated in heart failure cases compared with controls, signifying an adaptive stress response that is higher the more severe the disease. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.