biostudies-literatureQi LChina Scholarship CouncilNCCIH NIH HHSNHLBI NIH HHSNational Institute of HealthAmerican Diabetes AssociationNIGMS NIH HHS59-73https://www.ebi.ac.uk/biostudies/studies/S-EPMC7483359biostudies-literatureUnknown145Deubiquitinating enzymes (DUBs) appear to be a new class of regulators of cardiac homeostasis and disease. However, DUB-mediated signaling in the heart is not well understood. Herein we report a novel mechanism by which cylindromatosis (CYLD), a DUB mediates cardiac pathological remodeling and dysfunction. Cardiomyocyte-restricted (CR) overexpression of CYLD (CR-CYLD) did not cause gross health issues and hardly affected cardiac function up to age of one year in both female and male mice at physiological conditions. However, CR-CYLD overexpression exacerbated pressure overload (PO)-induced cardiac dysfunction associated with suppressed cardiac hypertrophy and increased myocardial apoptosis in mice independent of the gender. At the molecular level, CR-CYLD overexpression enhanced PO-inducedJournal of molecular and cellular cardiologyCYLD exaggerates pressure overload-induced cardiomyopathy via suppressing autolysosome efflux in cardiomyocytes.PMC7483359201506220204R01 HL0856291–16-IBS-059P20 GM103641R01 HL072166P01 AT003961R01 HL131667Qi LZang HNagarkatti MLiu QWang XWu WNagarkatti PRobbins JCui TfalseCYLD exaggerates pressure overload-induced cardiomyopathy via suppressing autolysosome efflux in cardiomyocytes.Deubiquitinating enzymes (DUBs) appear to be a new class of regulators of cardiac homeostasis and disease. However, DUB-mediated signaling in the heart is not well understood. Herein we report a novel mechanism by which cylindromatosis (CYLD), a DUB mediates cardiac pathological remodeling and dysfunction. Cardiomyocyte-restricted (CR) overexpression of CYLD (CR-CYLD) did not cause gross health issues and hardly affected cardiac function up to age of one year in both female and male mice at physiological conditions. However, CR-CYLD overexpression exacerbated pressure overload (PO)-induced cardiac dysfunction associated with suppressed cardiac hypertrophy and increased myocardial apoptosis in mice independent of the gender. At the molecular level, CR-CYLD overexpression enhanced PO-induced2020-01-01T00:00:00Z2020 Aug2026-05-07T15:15:34.208Z2022-02-11T00:44:53.787ZS-EPMC74833593255359410.1016/j.yjmcc.2020.06.004