Altogether, our results illustrate that LPS-mediated activation of DRP1-related mitochondrial fission through the JNK-LATS2 pathway participates in the pathogenesis of septic cardiomyopathy.
Altogether, our results define the Mst1/Drp1/mitochondrial fission/F-actin axis as a new signaling pathway that mediates LPS-related septic cardiomyopathy by inducing mitochondrial stress and cardiomyocyte death.
In the current preclinical study, we demonstrate the therapeutic potential of sarcospan (SSPN) overexpression to alleviate cardiomyopathy associated with Duchenne muscular dystrophy (DMD) utilizing dystrophin-deficient mdx mice with utrophin haploinsufficiency that more accurately represent the severe disease course of human DMD.
In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn<sup>-/-</sup>, or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age.
In contrast, mdx mice also lacking utrophin (utrn(-/-);mdx) show severely reduced cardiac contractile function and histological indicators of cardiomyopathy by 8-10weeks-of-age.