STING protects against cardiac dysfunction and remodelling by blocking autophagy

Area of Science:

• Cardiovascular Biology
• Immunology
• Cellular Biology

Background:

• Heart failure is a common chronic disease in the elderly, characterized by cardiac remodeling.
• Stimulator of interferon genes (STING) plays a role in immune response and inflammation.
• The role of STING in cardiomyopathy and cardiac remodeling remains largely unknown.

Purpose of the Study:

• To investigate the effect of STING on cardiac remodeling.
• To explore the potential mechanisms by which STING influences cardiac remodeling.

Main Methods:

• Constructed a mouse model of cardiac remodeling via aortic banding (AB) surgery.
• Utilized DNA microinjection to overexpress STING in mice.
• Evaluated cardiac hypertrophy, fibrosis, inflammation, and function in vivo and in vitro.
• Assessed autophagy levels and the effect of rapamycin on STING's cardioprotective effects.

Main Results:

• STING expression increased in AB-challenged mice.
• STING overexpression mitigated cardiac hypertrophy, fibrosis, inflammation, and improved cardiac function.
• STING inhibited Ang II-induced cardiomyocyte hypertrophy and TGF-β-induced cardiac fibroblast activation.
• STING overexpression reversed AB-induced autophagy activation, potentially via ULK1 phosphorylation.

Conclusions:

• STING may prevent pressure overload-induced cardiac remodeling by inhibiting autophagy.
• STING represents a potential therapeutic target for heart failure.