Small molecule STING inhibition improves myocardial infarction remodeling

Area of Science:

• Cardiovascular Research
• Immunology
• Pharmacology

Background:

• Myocardial infarction (MI) causes significant mortality globally.
• Inflammation post-MI is crucial for healing but can lead to adverse cardiac remodeling.
• The cGAS-STING pathway is implicated in innate immunity and has been shown to be active in MI.

Purpose of the Study:

• To investigate the translational potential of pharmacologic STING inhibition in a preclinical MI model.
• To determine if small-molecule STING inhibitors can mitigate adverse cardiac remodeling and improve outcomes after MI.

Main Methods:

• Utilized a murine MI model to test novel, selective small-molecule STING inhibitors.
• Assessed cardiac remodeling, infarct expansion, fibrosis, cardiomyocyte hypertrophy, and inflammatory gene expression.
• Administered STING inhibitors following reperfused MI.

Main Results:

• STING inhibition did not reduce mortality in non-reperfused MI.
• In reperfused MI, STING inhibition for three weeks decreased infarct expansion and scarring.
• Pharmacologic STING inhibition improved left ventricular systolic function and reduced cardiomyocyte hypertrophy.

Conclusions:

• Selective small-molecule STING inhibition shows potential for improving wound healing post-MI.
• STING inhibition may attenuate pathological remodeling and the development of ischemic heart failure.
• This approach offers a promising therapeutic strategy for managing heart failure after myocardial infarction.