Serum free thiols in chronic heart failure

Abstract

Oxidative stress is a key element of the pathophysiology of heart failure (HF). As free thiols are readily oxidized by reactive oxygen and sulfur species, their circulating level may directly reflect the systemic redox status. This study addresses the role of serum free thiols in chronic HF, which is of particular interest as free thiols are amenable to therapeutic modulation and thus are a potential target for therapy.Free thiols were measured in serum of 101 previously characterized stable chronic HF patients (93% male, age 63.7 ± 10.0 y, left ventricular ejection fraction 34.6 ± 8.2%), adjusted for total serum protein, and subsequently analysed for associations with clinical and outcome parameters.The mean serum free thiol concentration was 3.6 ± 0.5 μM/g protein. Patients with aboveaverage levels were younger, had better renal function, lower levels of NT-proBNP and PTH, and higher levels of cholesterol. Furthermore, above-average levels were associated with favourable disease outcome, i.e. a decreased rehospitalisation rate and increased patient survival (HR 0.27 (95% CI 0.11-0.62), P=0.002) independent of associated clinical parameters, age and PTH. After adjustment for cholesterol or established prognostic factors in HF, eGFR and NT-proBNP the association was no longer significant, suggesting involvement of these variables in a common pathophysiological pathway.This exploratory study demonstrates favourable associations of serum free thiols with markers of HF severity and prognosis as well as disease outcome, which should be further investigated in larger prospective studies. Restoring redox status by therapeutic modulation of free thiols may be a promising strategy to improve disease outcome in CHF.

Rapid free thiol rebound is a physiological response following cold‐induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

“…; Koning et al. ). Serum levels of ET‐1 were measured according to the manufacturer's instructions using commercially available Quantikine ELISA kits (DET10 R&D Systems, Abingdon, UK) as previously described (Jongman et al.…”

“…Moreover, in other conditions (e.g., chronic heart failure and renal transplantation) thiol depletion predicted mortality and disease outcome and was associated with cardiovascular disease (Koning et al. , ).…”

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

“…Another highly significant association was found between total free thiol status in serum and clinical outcome in unrelated clinical conditions (61, 105). Given the overall complexity of the extracellular antioxidant network and its link to intracellular redox status, the latter was utterly unexpected.…”

“…In renal transplant recipients, protein-adjusted serum-free thiols were found to predict graft failure and patient survival (61, 105). In a small cohort of stable chronic heart failure patients, there was a positive association between protein-adjusted serum-free thiols and a favorable disease outcome (61, 105).…”

“…In a small cohort of stable chronic heart failure patients, there was a positive association between protein-adjusted serum-free thiols and a favorable disease outcome (61, 105). Interestingly, a study evaluating the concentration of serum protein thiols in a wide range of species concluded that free thiol levels are positively associated with life span, suggesting that control of redox status has retained its importance from evolution to modern-day (patho)physiology (146).…”