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Glutaredoxin-1 levels in plasma can predict future events in patients with cardiovascular diseases
Yosuke Watanabe1, Takamitsu Nakamura1, Manabu Uematsu1
1Department of Cardiovascular Medicine, University of Yamanashi, Yamanashi, Japan.
Insights
Higher plasma levels of glutaredoxin-1 (Glrx) indicate a greater risk of adverse events in cardiovascular disease (CVD) patients. This finding suggests Glrx may serve as a prognostic biomarker for CVD.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Cardiovascular disease (CVD) is associated with increased reactive oxygen species, leading to protein S-glutathionylation.
- Glutaredoxin-1 (Glrx) removes glutathione adducts and plays a role in CVD models, but its clinical prognostic value in CVD patients is unclear.
- Glrx is detectable in human plasma and has been proposed as a potential disease marker for conditions including CVD.
Purpose of the Study:
- To investigate the association between plasma glutaredoxin-1 (Glrx) levels and the occurrence of future adverse events in patients with cardiovascular disease (CVD).
- To determine if Glrx can serve as a predictive biomarker for prognosis in CVD patients.
Main Methods:
- Plasma Glrx levels were quantified using enzyme-linked immunosorbent assay in 555 patients with CVD undergoing cardiac catheterization.
- Patients were prospectively followed for up to 36 months for adverse events, including death, myocardial infarction, and heart failure.
- Kaplan-Meier and multivariate Cox proportional hazards analyses were employed to assess the relationship between Glrx levels and adverse events.
Main Results:
- A total of 54 adverse events occurred during a mean follow-up of 33 months.
- Patients with higher plasma Glrx levels (>0.622 ng/mL) exhibited a significantly higher probability of experiencing adverse events compared to those with lower levels (P < 0.01).
- Multivariate analysis confirmed Glrx as a significant independent predictor of adverse events in CVD patients.
Conclusions:
- Plasma Glrx levels, particularly above 0.662 ng/mL, are associated with an increased risk of future adverse events in patients with cardiovascular disease.
- Glrx has potential as a prognostic biomarker for predicting adverse outcomes in the clinical setting of CVD.
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.
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