A possible role for proinflammatory activation via cGAS-STING pathway in atherosclerosis induced by accumulation of DNA double-strand breaks.

ABSTRACT: DNA damage contributes to atherosclerosis. However, causative links between DNA double-strand breaks (DSBs) and atherosclerosis have yet to be established. Here, we investigated the role of DSBs in atherosclerosis using mice and vascular cells deficient in Ku80, a DSB repair protein. After 4 weeks of a high-fat diet, Ku80-deficient apolipoprotein E knockout mice (Ku80^+/-ApoE^-/-) displayed increased plaque size and DSBs in the aorta compared to those of ApoE^-/- control. In the preatherosclerotic stages (two-week high-fat diet), the plaque size was similar in both the Ku80^+/-ApoE^-/- and ApoE^-/- control mice, but the number of DSBs and mRNA levels of inflammatory cytokines such as IL-6 and MCP-1 were significantly increased in

SUBMITTER: Sakai C 

PROVIDER: S-EPMC10542807 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature