IL-37 Modulates Myocardial Calcium Handling via the p-STAT3/SERCA2a Axis in HF-Related Engineered Human Heart Tissue

Area of Science:

• Cardiology
• Cell Biology
• Biochemistry

Background:

• Heart failure (HF) involves impaired cardiac function and inflammation.
• Interleukin-37 (IL-37) is an anti-inflammatory cytokine with potential therapeutic roles.
• Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) offer a model for studying cardiac disease.

Purpose of the Study:

• To investigate the regulatory mechanism of IL-37 in HF-related hiPSC-CMs and engineered heart tissue.
• To assess the reparative effects of IL-37 on cardiac function under stress conditions (hypoxia and H2O2).
• To elucidate the molecular pathway through which IL-37 exerts its beneficial effects.

Main Methods:

• Treatment of HF-related hiPSC-CMs and engineered heart tissue with IL-37.
• Assessment of cell viability, contractile force, and Ca2+ handling using specialized equipment.
• Analysis of protein expression and localization, including p-STAT3 and SERCA2a, and their interaction with the SERCA2a promoter.

Main Results:

• IL-37 significantly improved cell viability, calcium transient levels, and contractile force in stressed hiPSC-CMs and engineered heart tissue.
• IL-37 treatment led to enhanced Ca2+ conduction capacity.
• IL-37 upregulated SERCA2a expression by increasing nuclear p-STAT3 levels, which bound to the SERCA2a promoter.

Conclusions:

• IL-37 possesses significant reparative effects on HF-related cardiac cells and tissues.
• The p-STAT3/SERCA2a signaling axis is a key mechanism mediating IL-37's beneficial effects on myocardial calcium handling.
• IL-37 shows promise as a therapeutic agent for enhancing systolic function in heart failure.