{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:45:54Z","timestamp":1792665954655,"version":"4.5.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,6,27]]},"abstract":"<jats:p>\n                    Heart failure is accompanied by important defects in metabolism. The transcriptional coactivator peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1) is a powerful regulator of mitochondrial biology and metabolism. PGC-1\u03b1 and numerous genes regulated by PGC-1\u03b1 are repressed in models of cardiac stress, such as that generated by transverse aortic constriction (TAC). This finding has suggested that PGC-1\u03b1 repression may contribute to the maladaptive response of the heart to chronic hemodynamic loads. We show here that TAC in mice genetically engineered to lack PGC-1\u03b1 leads to accelerated cardiac dysfunction, which is accompanied by signs of significant clinical heart failure. Treating cardiac cells in tissue culture with the catecholamine epinephrine leads to repression of PGC-1\u03b1 and many of its target genes, recapitulating the findings\n                    <jats:italic>in vivo<\/jats:italic>\n                    in response to TAC. Importantly, introduction of ectopic PGC-1\u03b1 can reverse the repression of most of these genes by epinephrine. Together, these data indicate that endogenous PGC-1\u03b1 serves a cardioprotective function and suggest that repression of PGC-1\u03b1 significantly contributes to the development of heart failure. Moreover, the data suggest that elevating PGC-1\u03b1 activity may have therapeutic potential in the treatment of heart failure.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0603615103","type":"journal-article","created":{"date-parts":[[2006,6,14]],"date-time":"2006-06-14T21:00:31Z","timestamp":1150318831000},"page":"10086-10091","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":343,"title":["Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-\u03b3 coactivator 1\u03b1"],"prefix":"10.1073","volume":"103","author":[{"given":"Zoltan","family":"Arany","sequence":"first","affiliation":[{"name":"*Dana\u2013Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Novikov","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry","family":"Chin","sequence":"additional","affiliation":[{"name":"*Dana\u2013Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Ma","sequence":"additional","affiliation":[{"name":"*Dana\u2013Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Spiegelman","sequence":"additional","affiliation":[{"name":"*Dana\u2013Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,6,27]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"e85","volume":"113","author":"Thom T.","year":"2006","unstructured":"T. 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