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dc.contributor.authorGarcía-Pelagio, K.P.
dc.contributor.authorChen, L.
dc.contributor.authorJoca, H.C.
dc.date.accessioned2019-05-17T13:21:16Z
dc.date.available2019-05-17T13:21:16Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85039416157&doi=10.1016%2fj.yjmcc.2017.12.005&partnerID=40&md5=7506d928d9718aa4f7d8dc6d7ffd7e6c
dc.identifier.urihttp://hdl.handle.net/10713/9185
dc.description.abstractCardiomyopathies have been linked to changes in structural proteins, including intermediate filament (IF) proteins located in the cytoskeleton. IFs associate with the contractile machinery and costameres of striated muscle and with intercalated disks in the heart. Synemin is a large IF protein that mediates the association of desmin with Z-disks and stabilizes intercalated disks. It also acts as an A-kinase anchoring protein (AKAP). In murine skeletal muscle, the absence of synemin causes a mild myopathy. Here, we report that the genetic silencing of synemin in mice (synm −/−) causes left ventricular systolic dysfunction at 3 months and 12-16 months of age, and left ventricular hypertrophy and dilatation at 12-16 months of age. Isolated cardiomyocytes showed alterations in calcium handling that indicate defects intrinsic to the heart. Although contractile and costameric proteins remained unchanged in the old synm -/- hearts, we identified alterations in several signaling proteins (PKA-RII, ERK and p70S6K) critical to cardiomyocyte function. Our data suggest that synemin plays an important regulatory role in the heart and that the consequences of its absence are profound. Copyright 2017 The Author(s)en_US
dc.description.sponsorshipOur research has been supported in part by a Physiological Genomics Fellowship-APS and UNAM-PAPIIT ( IA 209016 ) to KPGP, by a CNPq / CAPES -Science without Borders Scholarship to HCJ, by a donation from the Kahlert Foundation and by grants from the National Institutes of Health to CWW ( R01 AR062554 ), WJL ( R01 HL105239 , U01 HL116321 ), and RJB ( R01 AR 055928 ).en_US
dc.description.urihttps://dx.doi.org/10.1016/j.yjmcc.2017.12.005en_US
dc.language.isoen_USen_US
dc.publisherAcademic Pressen_US
dc.relation.ispartofJournal of Molecular and Cellular Cardiology
dc.subjectAKAPsen_US
dc.subjectCostameresen_US
dc.subjectHypertrophic and dilated cardiomyopathyen_US
dc.subjectIntermediate filamenten_US
dc.subjectMuscular dystrophyen_US
dc.titleAbsence of synemin in mice causes structural and functional abnormalities in hearten_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.yjmcc.2017.12.005


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