Inhibition of STING pathway attenuates experimental abdominal aortic aneurysm progression

Abdominal aortic aneurysm (AAA) is a chronic, inflammatory and degenerative vascular disease. Previous studies have demonstrated that stimulator of interferon genes (STING) is involved in multiple inflammatory diseases. However, the role of STING in AAA formation and its possible mechanisms have yet to be investigated. Here, we investigated the role of STING in the development of AAA using two murine AAA models induced by porcine pancreatic elastase (PPE)/β-aminopropionitrile (BAPN) or angiotensin II (Ang II). The STING signaling pathway was significantly activated in AAA tissues from both mice and patients. Sting mutation slowed AAA formation, as confirmed by reduced AAA incidence, maximal abdominal aortic diameter, elastin disruption, collagen deposition, and inhibited immune cell infiltration in AAA mice. RNA-sequencing analysis revealed that compared with the control, Sting mutation inhibited inflammatory and immune responses in AAA tissues. Similar effects were observed after pharmacological inhibition of STING in Ang II infused ApoE^-/- mice. Besides, STING signaling pathway was also activated in TNFα treated MOVAS. Sting knockdown suppressed inflammatory response and oxidative stress in vitro. Finally, colchicine protected against AAA formation in mice partially through inhibition of the STING signaling pathway. Our study demonstrated that Sting mutation and pharmacological inhibition could limit AAA progression possibly through inhibition of inflammation and oxidative stress. Colchicine could slow AAA formation in a partially STING-dependent manner in AAA mice. These findings suggest that STING might be a potential pharmacological target for the treatment of AAA.