Elevated Circulating Levels of Thioredoxin and Stress in Chronic Heart Failure

Background: 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.