Inhibition of STING pathway attenuates experimental abdominal aortic aneurysm progression

Area of Science:

• Vascular Biology
• Immunology
• Pharmacology

Background:

• Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation and degeneration.
• The stimulator of interferon genes (STING) pathway is implicated in various inflammatory conditions, but its role in AAA remains unclear.

Purpose of the Study:

• To investigate the role of STING in AAA formation and elucidate its underlying mechanisms.
• To evaluate STING as a potential therapeutic target for AAA treatment.

Main Methods:

• Murine AAA models induced by porcine pancreatic elastase/β-aminopropionitrile or angiotensin II were utilized.
• STING signaling activation was assessed in AAA tissues from mice and patients.
• STING knockout/mutation and pharmacological inhibition were employed.
• RNA-sequencing and in vitro assays (TNFα-treated MOVAS) were performed.
• The effect of colchicine on AAA formation was evaluated.

Main Results:

• STING signaling was significantly activated in AAA tissues.
• STING deficiency or inhibition reduced AAA incidence, aortic diameter, elastin disruption, collagen deposition, and immune cell infiltration.
• STING mutation suppressed inflammatory and immune responses.
• Pharmacological STING inhibition and STING knockdown reduced inflammation and oxidative stress.
• Colchicine demonstrated protective effects against AAA formation, partly via STING inhibition.

Conclusions:

• STING signaling is crucial for AAA development and progression.
• Targeting STING, either genetically or pharmacologically, can limit AAA progression by mitigating inflammation and oxidative stress.
• Colchicine may exert its protective effects in AAA partially through the STING pathway, highlighting STING as a promising therapeutic target.