Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced...

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Volume overload (VO) is a significant risk factor for cardiac morbidity and mortality.
• Cardiac dysfunction is exacerbated by aging, metabolic issues, and imbalanced cellular redox.
• Understanding early pathological changes in VO is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the early pathological mechanisms of cardiac remodeling in response to volume overload.
• To assess the role of oxidative stress and protein quality control in VO-induced cardiac dysfunction.
• To evaluate the therapeutic potential of glutathione in reversing VO-induced cardiac alterations.

Main Methods:

• Volume overload was induced in Wistar rats via an aortocaval fistula.
• Functional parameters were assessed using transthoracic echocardiography.
• Oxidative stress markers, protein quality control markers (heat shock proteins, caspases), and titin oxidation were analyzed.

Main Results:

• VO induced cardiac hypertrophy, mechanical dysfunction, and increased cardiomyocyte stiffness.
• Elevated oxidative stress markers and impaired protein quality control were observed.
• Glutathione treatment demonstrated a reversal of cardiac dysfunction and associated pathological markers.
• Inflammatory signaling pathways remained unchanged, suggesting a primary role for oxidative stress.

Conclusions:

• Early cardiac response to VO involves mechanical dysfunction and dysregulated signaling pathways.
• Enhanced oxidative stress and impaired protein quality control are key contributors to VO-induced cardiac pathology.
• Glutathione shows promise as a therapeutic agent for mitigating VO-induced cardiac damage.