{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:55:15Z","timestamp":1787237715035,"version":"build-2736575974"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"39","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,9,26]]},"abstract":"<jats:p>\n                    An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiomyocytes, the transcription factor\n                    <jats:italic>Gata4<\/jats:italic>\n                    is required for agonist-induced hypertrophy. We hypothesized that, in the intact organism,\n                    <jats:italic>Gata4<\/jats:italic>\n                    is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of\n                    <jats:italic>Gata4<\/jats:italic>\n                    (\n                    <jats:italic>G4D<\/jats:italic>\n                    ). At baseline,\n                    <jats:italic>G4D<\/jats:italic>\n                    mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC),\n                    <jats:italic>G4D<\/jats:italic>\n                    mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls,\n                    <jats:italic>G4D<\/jats:italic>\n                    -TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed up-regulation of genes associated with apoptosis and fibrosis, including members of the TGF-\u03b2 pathway. Our data demonstrate that\n                    <jats:italic>Gata4<\/jats:italic>\n                    is essential for cardiac function in the postnatal heart. After pressure overload,\n                    <jats:italic>Gata4<\/jats:italic>\n                    regulates the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced failure.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0602543103","type":"journal-article","created":{"date-parts":[[2006,9,18]],"date-time":"2006-09-18T20:57:41Z","timestamp":1158613061000},"page":"14471-14476","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":167,"title":["Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure"],"prefix":"10.1073","volume":"103","author":[{"given":"Egbert","family":"Bisping","sequence":"first","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadakatsu","family":"Ikeda","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sek Won","family":"Kong","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Tarnavski","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Bodyak","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"McMullen","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Son","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangli","family":"Springer","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Kang","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Izumo","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Pu","sequence":"additional","affiliation":[{"name":"*Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,9,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/415227a"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/16.suppl_O.110"},{"key":"e_1_3_4_3_2","first-page":"10","volume-title":"Heart Failure: A Companion to Braunwald's Heart Disease","author":"Izumo S","year":"2004","unstructured":"S Izumo, WT Pu Heart Failure: A Companion to Braunwald's Heart Disease, ed DL Mann (Saunders, Philadelphia), pp. 10\u201340 (2004)."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.03.025"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R000029200"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102174200"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302719200"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.8.1048"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.8.1061"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23769"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.08.008"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00041.2003"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401833101"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.20.7550-7558.2000"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119730"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.9.1007"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.1999.00822.x"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.21.7460-7469.2001"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.4.753"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.11.2757"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000062465.60601.CC"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1427"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.12.2387"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000129254.25507.d6"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1299.032"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000137836.95625.D4"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.02.021"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.05.012"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162370099"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000161873.27088.4c"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81460-9"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000215985.18538.c4"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2003.07.007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00004.2004"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310405200"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.11.2537"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00226.2004"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0602543103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:54:09Z","timestamp":1649775249000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0602543103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,26]]},"references-count":37,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2006,9,26]]}},"alternative-id":["10.1073\/pnas.0602543103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0602543103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,26]]},"assertion":[{"value":"2006-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-09-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}