Absence of synemin in mice causes structural and functional abnormalities in heart
JournalJournal of Molecular and Cellular Cardiology
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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)
SponsorsOur 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 ).
Hypertrophic and dilated cardiomyopathy
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85039416157&doi=10.1016%2fj.yjmcc.2017.12.005&partnerID=40&md5=7506d928d9718aa4f7d8dc6d7ffd7e6c; http://hdl.handle.net/10713/9185