{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:41:53Z","timestamp":1790779313566,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,4,11]]},"abstract":"<jats:p>\n                    Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients and sarcoplasmic reticulum (SR) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger, \u03b2-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0601072103","type":"journal-article","created":{"date-parts":[[2006,4,4]],"date-time":"2006-04-04T20:34:38Z","timestamp":1144182878000},"page":"6043-6048","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction"],"prefix":"10.1073","volume":"103","author":[{"given":"Maria Giovanna","family":"Trivieri","sequence":"first","affiliation":[{"name":"*Heart and Stroke\/Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2;"},{"name":"Division of Cardiology, University Health Network, Toronto, ON, Canada M5S 3E2;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin Y.","family":"Oudit","sequence":"additional","affiliation":[{"name":"*Heart and Stroke\/Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2;"},{"name":"Division of Cardiology, University Health Network, Toronto, ON, Canada M5S 3E2;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan","family":"Sah","sequence":"additional","affiliation":[{"name":"*Heart and Stroke\/Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2;"},{"name":"Division of Cardiology, University Health Network, Toronto, ON, Canada M5S 3E2;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit-Gilles","family":"Kerfant","sequence":"additional","affiliation":[{"name":"*Heart and Stroke\/Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2;"},{"name":"Division of Cardiology, University Health Network, Toronto, ON, Canada M5S 3E2;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"*Heart and Stroke\/Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2;"},{"name":"Division of Cardiology, University Health Network, Toronto, ON, Canada M5S 3E2;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"O. 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