In a mouse aortic aneurysm model, single-cell sequencing revealed that increased STING expression in smooth muscle and macrophage subpopulations led to smooth muscle death and dsDNA release, which activated the macrophage STING-TBK1-IRF3 pathway, leading to increased expression of matrix metalloproteinases (MMPs), which degrade the ECM. Here, STING1 is linked to aortic aneurysm.