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Studies showed that overexpression of FKBP12.6 attenuated thoracic aortic constriction (TAC)\u2010induced cardiac hypertrophy in mice, whereas the adenovirus\u2010mediated overexpression of FKBP12.6 induced hypertrophy and apoptosis in cultured neonatal cardiomyocytes, indicating that the role of FKBP12.6 in cardiac hypertrophy is still controversial. In this study, we aimed to investigate the roles and mechanisms of FKBP12.6 in angiotensin II (AngII)\u2010induced cardiac hypertrophy using various transgenic mouse models in\u00a0vivo and in\u00a0vitro. FKBP12.6 knockout (FKBP12.6<jats:sup>\u2212\/\u2212<\/jats:sup>) mice and cardiac\u2010specific FKBP12.6 overexpressing (FKBP12.6 TG) mice were infused with AngII (1500\u00a0ng\/kg\/min) for 14\u00a0days subcutaneously by implantation of an osmotic mini\u2010pump. The results showed that FKBP12.6 deficiency aggravated AngII\u2010induced cardiac hypertrophy, while cardiac\u2010specific overexpression of FKBP12.6 prevented hearts from the hypertrophic response to AngII stimulation in mice. Consistent with the results in\u00a0vivo, overexpression of FKBP12.6 in H9c2 cells significantly repressed the AngII\u2010induced cardiomyocyte hypertrophy, seen as reductions in the cell sizes and the expressions of hypertrophic genes. Furthermore, we demonstrated that the protection of FKBP12.6 on AngII\u2010induced cardiac hypertrophy was involved in reducing the concentration of intracellular Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]i), in which the protein significantly inhibited the key Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent signalling pathways such as calcineurin\/cardiac form of nuclear factor of activated T cells 4 (NFATc4), calmodulin kinaseII (CaMKII)\/MEF\u20102, AKT\/Glycogen synthase kinase 3\u03b2 (GSK3\u03b2)\/NFATc4 and AKT\/mTOR signalling pathways. Our study demonstrated that FKBP12.6 protects heart from AngII\u2010induced cardiac hypertrophy through inhibiting Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010mediated signalling pathways.<\/jats:p>","DOI":"10.1111\/jcmm.13645","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T06:31:37Z","timestamp":1524465097000},"page":"3638-3651","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["FKBP12.6 protects heart from AngII\u2010induced hypertrophy through inhibiting Ca<sup>2+<\/sup>\/calmodulin\u2010mediated signalling pathways in\u00a0vivo and in\u00a0vitro"],"prefix":"10.1111","volume":"22","author":[{"given":"Yun\u2010Fei","family":"Xiao","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine Nanchang University Nanchang China"},{"name":"School of Life Science Nanchang University Nanchang 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