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Published on: June 28, 2024
Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities
Thibaud Damy1, Matthias Kirsch, Lara Khouzami
1Département de Chirurgie Cardiaque, AP-HP, Groupe Hospitalier Henri-Mondor Albert-Chenevier, Fédération de Cardiologie, Créteil, France.
Insights
Glutathione deficiency in the heart and blood is linked to heart disease severity and functional decline. Blood glutathione levels may serve as an early biomarker for detecting asymptomatic cardiac abnormalities.
Area of Science:
- Cardiology
- Biochemistry
- Biomarkers
Background:
- Glutathione (L-gamma-glutamyl-cysteinyl-glycine) is vital for cell survival.
- Deficiency in cardiac and systemic glutathione is associated with heart failure progression and cardiac remodeling in animal models.
Purpose of the Study:
- To investigate cardiac and blood glutathione levels in patients with varying functional classes and structural heart diseases.
- To explore the relationship between glutathione levels and heart disease severity.
Main Methods:
- Glutathione was measured using an enzymatic recycling method in blood samples from 91 individuals (15 healthy, 76 patients).
- Glutathione was quantified in right atrial appendages from patients undergoing cardiac surgery.
- Patients were categorized by New York Heart Association (NYHA) functional class (I-IV) and cardiac conditions (coronary artery disease, aortic stenosis, cardiomyopathy).
Main Results:
- Cardiac glutathione was significantly depleted (-58%) in NYHA class IV patients compared to class I.
- In coronary artery disease patients, glutathione depletion correlated with left ventricular dysfunction severity.
- Blood glutathione was reduced by 21% in NYHA class I patients and 40% in symptomatic patients (NYHA class II-IV) compared to controls.
- Blood glutathione depletion preceded elevation of sTNFR1, a marker of symptomatic heart failure.
Conclusions:
- Cardiac and systemic glutathione deficiency correlates with functional status and structural abnormalities in cardiac patients.
- Blood glutathione testing may be a novel biomarker for detecting asymptomatic patients with structural cardiac abnormalities.
Background:
The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases.
Methods:
Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery.
Results:
In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P<0.01), and by 40% in symptomatic patients of NYHA class II to IV (P<0.0001). According to the functional NYHA class, significant depletion in blood glutathione occurred before detectable elevation in blood sTNFR1, a marker of symptomatic heart failure severity, as shown by the exponential relationship between these two parameters in the whole cohort of patients (r = 0.88).
Conclusions:
This study provides evidence that cardiac and systemic glutathione deficiency is related to the functional status and structural cardiac abnormalities of patients with cardiac diseases. These data also suggest that blood glutathione test may be an interesting new biomarker to detect asymptomatic patients with structural cardiac abnormalities.
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