Glutaredoxin-1 levels in plasma can predict future events in patients with cardiovascular diseases

Abstract

Reactive oxygen species that increase during cardiovascular disease (CVD) react with protein cysteine residues to form a glutathione adduct by S-glutathionylation, which is selectively removed by glutaredoxin-1 (Glrx). We previously showed that S-glutathionylation and Glrx play important roles in mouse models of CVD, such as heart failure and peripheral artery disease models. However, there are few clinical studies on Glrx in CVD. Although Glrx is a cytosolic protein expressed in various organs, it is detectable in human plasma. Studies have reported that Glrx in plasma is a potential disease maker, such as CVD and chronic kidney disease and diabetes, however, it remains unclear whether Glrx is related to the prognosis of patients with CVD. The purpose of this study was to elucidate whether Glrx levels in plasma are associated with future events in patients with CVD. Plasma levels of Glrx were measured in 555 patients with CVD who underwent cardiac catheterization using enzyme-linked immunosorbent assay. All patients were followed prospectively for ≤36 months or until occurrence of adverse events, including all-cause death, non-fatal myocardial infarction, and worsening heart failure. During a mean follow-up period of 33 months, 54 adverse events occurred. Kaplan-Meier analysis showed that higher levels of Glrx (>0.622 ng/mL, determined by receiver-operating characteristic curve) resulted in a higher probability for adverse events compared with lower levels of Glrx (≤0.622 ng/mL) (P < 0.01, log-rank test). Multivariate Cox proportional hazards analysis showed that Glrx was a significant predictor of adverse events after adjustment for known risk factors. In conclusion, levels of plasma Glrx >0.662 ng/mL can predict future events in patients with CVD.