Selective Connexin43 Inhibition Prevents Isoproterenol-Induced Arrhythmias and Lethality in Muscular Dystrophy Mice.

ABSTRACT: Duchenne muscular dystrophy (DMD) is caused by an X-linked mutation that leads to the absence of dystrophin, resulting in life-threatening arrhythmogenesis and associated heart failure. We targeted the gap junction protein connexin43 (Cx43) responsible for maintaining cardiac conduction. In mild mdx and severe mdx:utr mouse models of DMD, and human DMD tissues, Cx43 was found to be pathologically mislocalized to lateral sides of cardiomyocytes. In addition, overall Cx43 protein levels were markedly increased in mouse and human DMD heart tissues examined. Electrocardiography on isoproterenol challenged mice showed that both models developed arrhythmias and died within 24 hours, while wild-type mice were free of pathology. Administering peptide mimetics to inhibit lateralized Cx43 function p

SUBMITTER: Gonzalez JP 

PROVIDER: S-EPMC4550874 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature