Radiation speeds up plaque growth through a macrophage mtDNA–cGAS–STING–NLRP3 loop
- Ionising radiation worsened atherosclerosis in ApoE-knockout mice, with more pyroptosis-related gene expression in plaque macrophages.
- Radiation drove mitochondrial DNA into the cytoplasm, activating cGAS/STING/TBK1; phosphorylated IRF3 then bound the NLRP3 promoter and raised its transcription.
- Caspase-1 deletion or macrophage-specific cGAS knockdown blunted the radiation effect.
💡 Points Based on the abstract
The genetic arms are convincing for the mechanism, but nobody has yet shown a pharmacological intervention: a STING or NLRP3 inhibitor given after irradiation would tell us whether this is druggable or just explanatory. STING inhibitors also carry a theoretical risk for the very antitumour immunity radiotherapy relies on, so any translation has to protect the heart without blunting the tumour response.
📄 Paper · British Journal of Pharmacology ↗ Mitochondrial DNA-cGAS-STING induces macrophage pyroptosis via phospho-IRF3-mediated NLRP3 expression in ionising radiation-induced atherosclerosis progression