{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:49:28Z","timestamp":1791265768060,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T00:00:00Z","timestamp":1248912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>Cardiomyocyte hypertrophy occurs in response to a variety of physiological and pathological stimuli. While pathological hypertrophy in heart failure is usually coupled with depressed contractile function, physiological hypertrophy associates with increased contractility. In the present study, we explored whether 8 weeks of moderate intensity exercise training would lead to a cardiac anti\u2010remodelling effect in an experimental model of heart failure associated with a deactivation of a pathological (calcineurin\/NFAT, CaMKII\/HDAC) or activation of a physiological (Akt\u2013mTOR) hypertrophy signalling pathway. The cardiac dysfunction, exercise intolerance, left ventricle dilatation, increased heart weight and cardiomyocyte hypertrophy from mice lacking \u03b1<jats:sub>2A<\/jats:sub> and \u03b1<jats:sub>2C<\/jats:sub> adrenoceptors (\u03b1<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2C<\/jats:sub>ARKO mice) were associated with sympathetic hyperactivity induced heart failure. The relative contribution of Ca<jats:sup>2+<\/jats:sup>\u2013calmodulin high\u2010affinity (calcineurin\/NFAT) and low\u2010affinity (CaMKII\/HDAC) targets to pathological hypertrophy of \u03b1<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2C<\/jats:sub>ARKO mice was verified. While nuclear calcineurin B, NFATc3 and GATA\u20104 translocation were significantly increased in \u03b1<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2C<\/jats:sub>ARKO mice, no changes were observed in CaMKII\/HDAC activation. As expected, cyclosporine treatment decreased nuclear translocation of calcineurin\/NFAT in \u03b1<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2C<\/jats:sub>ARKO mice, which was associated with improved ventricular function and a pronounced anti\u2010remodelling effect. The Akt\/mTOR signalling pathway was not activated in \u03b1<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2C<\/jats:sub>ARKO mice. Exercise training improved cardiac function and exercise capacity in \u03b1<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2C<\/jats:sub>ARKO mice and decreased heart weight and cardiomyocyte width paralleled by diminished nuclear NFATc3 and GATA\u20104 translocation as well as GATA\u20104 expression levels. When combined, these findings support the notion that deactivation of calcineurin\/NFAT pathway\u2010induced pathological hypertrophy is a preferential mechanism by which exercise training leads to the cardiac anti\u2010remodelling effect in heart failure.<\/jats:p>","DOI":"10.1113\/jphysiol.2009.173948","type":"journal-article","created":{"date-parts":[[2009,6,9]],"date-time":"2009-06-09T00:46:59Z","timestamp":1244508419000},"page":"3899-3910","source":"Crossref","is-referenced-by-count":56,"title":["Cardiac anti\u2010remodelling effect of aerobic training is associated with a reduction in the calcineurin\/NFAT signalling pathway in heart failure mice"],"prefix":"10.1113","volume":"587","author":[{"given":"R. S. F.","family":"Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C. B.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. R. 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