Does reversible cysteine oxidation link the Western diet to cardiac dysfunction?

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Metabolomics

Background:

• Metabolic syndrome is linked to diastolic dysfunction, a condition affecting heart relaxation.
• Oxidative stress and protein modification play roles in cardiovascular diseases.
• Understanding molecular changes in the heart is crucial for treating diastolic dysfunction.

Purpose of the Study:

• To investigate global changes in reversible cysteine oxidation in the heart's left ventricle of mice with diet-induced metabolic syndrome.
• To identify specific proteins affected by altered cysteine oxidation due to metabolic syndrome.
• To explore the potential impact of these modifications on cardiac function and energy metabolism.

Main Methods:

• A novel cysteine thiol labeling strategy was employed.
• Mass spectrometric analysis was used for protein identification and quantification.
• Mice were fed a high-fat, high-sucrose diet for 8 months to induce metabolic syndrome and diastolic dysfunction.

Main Results:

• 173 proteins with quantifiable reversible thiol oxidation were identified.
• 98 of these proteins showed differential cysteine modification (≥1.5-fold) due to the diet.
• Diet-induced metabolic syndrome caused significant changes in protein oxidation in the left ventricle.

Conclusions:

• Metabolic syndrome induces potentially harmful changes in the oxidative modification of metabolically active proteins in the heart.
• These alterations may negatively regulate energy substrate flux through key metabolic pathways (glycolysis, beta-oxidation, TCA cycle, oxidative phosphorylation).
• Modified protein oxidation may contribute to maladaptive tissue remodeling and diastolic left ventricular dysfunction.