Blocking cGAS-STING in vessel walls curbs aortic aneurysm in mice
- Single-cell data from mouse and human aneurysm tissue place cGAS-STING signaling mainly in endothelial cells, with higher expression in ruptured than stable human lesions.
- In angiotensin II-driven mouse aneurysm, the pathway was switched on; either a cGAS inhibitor or a STING antagonist lowered aneurysm occurrence and tissue damage and improved endothelial mitochondria.
- Patient aneurysm samples also showed elevated pathway proteins, and DHFR loss emerged as a possible link between DNA damage and activation.
💡 Points Based on the abstract
Two inhibitors, one mouse model: that's thin. Angiotensin II aneurysm is acute and hypertension-driven, a poor mimic of slow human AAA, and RU.521 is far more potent on mouse than human cGAS. Human evidence is correlative expression, not genetics. Next study needs dosing after aneurysm is established, exposure data, and a second model such as elastase.