Lipopolysaccharide-induced DNA damage response activates DNA-PKcs to drive actin cytoskeleton disruption and cardiac microvascular dysfunction in endotoxemia

Our findings suggest that LPS triggers a DNA-PKcs-dependent DDR that promotes mitochondrial fragmentation and actin disruption, particularly in cardiac ECs, contributing to sepsis-induced cardiomyopathy. Targeting DNA-PKcs or mitochondrial fission may hold therapeutic potential for the treatment of sepsis-induced cardiomyopathy.