Understanding the intricate mechanisms underlying these pathological processes is crucial for developing effective therapeutic strategies to mitigate the harmful effects of I/R.1,2 Studies have reported that circulating levels of DNA were significantly elevated following cardiac ischemia.36 We further confirmed that during I/R injury, there occurs a profound degree of DNA damage, resulting in the leakage of DNA into the cytosol, subsequently triggering the upregulation of the cGAS-STING signaling pathway in CMs rather than fibroblasts or macrophages during acute I/R injury. Here, CGAS is linked to myocardial ischemia.