Since cofilin2 contains Ser/Thr residues amenable to phosphorylation by DNA-PKCs, we generated gene knockout and knockin mice and conducted in vivo and cell-based assays to test the hypothesis that DNA-PKcs promotes endotoxemia-related endothelial dysfunction and myocardial microvascular disorder by inducing cofilin2-dependent actin cytoskeleton remodeling. This evidence concerns the gene PRKDC and serum lipopolysaccharide activity.