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Syndecan-4 is a transmembrane heparan sulphate proteoglycan which is found increased in the myocardium of AS patients and AB mice. The role of syndecan-4 in cardiomyocyte hypertrophy is not well understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Purpose of the study<\/jats:title>\n                <jats:p>We developed mice with cardiomyocyte-specific overexpression of syndecan-4 (<jats:italic>Sdc4-Tg<\/jats:italic>) and subjected these to AB to examine the role of syndecan-4 in hypertrophy and activation of the pro-hypertrophic calcineurin-NFAT signalling pathway.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods and results<\/jats:title>\n                <jats:p><jats:italic>Sdc4-Tg<\/jats:italic> mice showed exacerbated cardiac remodelling upon AB compared to wild type (WT). At 2\u20136 weeks post-AB, <jats:italic>Sdc4-Tg<\/jats:italic> and WT mice showed similar hypertrophic growth, while at 20\u00a0weeks post-AB, exacerbated hypertrophy and dysfunction were evident in <jats:italic>Sdc4-Tg<\/jats:italic> mice. After cross-breeding of <jats:italic>Sdc4-Tg<\/jats:italic> mice with NFAT-luciferase reporter mice, we found increased NFAT activation in <jats:italic>Sdc4-Tg<\/jats:italic> hearts after AB. Immunoprecipitation showed that calcineurin bound to syndecan-4 in <jats:italic>Sdc4-Tg<\/jats:italic> hearts. Isolated cardiomyocytes from <jats:italic>Sdc4-Tg<\/jats:italic> mice showed alterations in Ca<jats:sup>2+<\/jats:sup> fluxes, suggesting that syndecan-4 regulated Ca<jats:sup>2+<\/jats:sup> levels, and thereby, activating the syndecan-4-calcineurin complex resulting in NFAT activation and hypertrophic growth. Similarly, primary cardiomyocyte cultures from neonatal rats showed increased calcineurin-NFAT-dependent hypertrophic growth upon viral <jats:italic>Sdc4<\/jats:italic> overexpression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study of mice with cardiomyocyte-specific overexpression of <jats:italic>Sdc4<\/jats:italic> have revealed that syndecan-4 is important for activation of the Ca<jats:sup>2+<\/jats:sup>-dependent calcineurin-NFAT signalling pathway, hypertrophic remodelling and dysfunction in cardiomyocytes in response to pressure overload.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11033-022-07985-y","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T15:57:24Z","timestamp":1665158244000},"page":"11795-11809","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cardiomyocyte-specific overexpression of syndecan-4 in mice results in activation of calcineurin-NFAT signalling and exacerbated cardiac hypertrophy"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9502-6841","authenticated-orcid":false,"given":"Ida G.","family":"Lunde","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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