Dipak Panigrahy, Abigail Kelly, Weicang Wang, Jun Yang, Sung Hee Hwang, Michael Gillespie, Isabella Howard, Carlos Bueno-Beti, Angeliki Asimaki, Vinay Penna, Kory Lavine, Matthew Edin, Darryl Zeldin, Bruce Hammock, Jeffrey Saffitz
Previous studies have implicated persistent innate immune signaling in the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a familial non-ischemic heart muscle disease characterized by life-threatening arrhythmias and progressive myocardial injury. Here, we provide new evidence implicating inflammatory lipid autocoids in ACM. We show that specialized pro-resolving lipid mediators are reduced in hearts of Dsg2mut/mut mice, a well characterized mouse model of ACM. We also found that ACM disease features can be reversed in rat ventricular myocytes expressing mutant JUP by the pro-resolving epoxy fatty acid (EpFA) 14,15-eicosatrienoic acid (14-15-EET), whereas 14,15-EE-5(Z)E which antagonizes actions of the putative 14,15-EET receptor, intensified nuclear accumulation of the desmosomal protein plakoglobin...
February 19, 2024: bioRxiv