{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:56:04Z","timestamp":1793224564135,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,10,15]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The transcriptional code that programs maladaptive cardiac hypertrophy involves the zinc finger\u2013containing DNA binding factor GATA-4. The highly related transcription factor GATA-6 is also expressed in the adult heart, although its role in controlling the hypertrophic program is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To determine the role of GATA-6 in cardiac hypertrophy and homeostasis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Here, we performed a cardiomyocyte-specific conditional gene targeting approach for\n              <jats:italic>Gata6<\/jats:italic>\n              , as well as a transgenic approach to overexpress GATA-6 in the mouse heart. Deletion of\n              <jats:italic>Gata6-loxP<\/jats:italic>\n              with\n              <jats:italic>Nkx2.5-cre<\/jats:italic>\n              produced late embryonic lethality with heart defects, whereas deletion with \u03b2-myosin heavy chain-cre (\u03b2MHC-cre) produced viable adults with &gt;95% loss of GATA-6 protein in the heart. These latter mice were subjected to pressure overload\u2013induced hypertrophy for 2 and 6 weeks, which showed a significant reduction in cardiac hypertrophy similar to that observed\n              <jats:italic>Gata4<\/jats:italic>\n              heart-specific deleted mice.\n              <jats:italic>Gata6<\/jats:italic>\n              -deleted mice subjected to pressure overload also developed heart failure, whereas control mice maintained proper cardiac function.\n              <jats:italic>Gata6<\/jats:italic>\n              -deleted mice also developed less cardiac hypertrophy following 2 weeks of angiotensin II\/phenylephrine infusion. Controlled GATA-6 overexpression in the heart induced hypertrophy with aging and predisposed to greater hypertrophy with pressure overload stimulation. Combinatorial deletion of\n              <jats:italic>Gata4<\/jats:italic>\n              and\n              <jats:italic>Gata6<\/jats:italic>\n              from the adult heart resulted in dilated cardiomyopathy and lethality by 16 weeks of age. Mechanistically, deletion of\n              <jats:italic>Gata6<\/jats:italic>\n              from the heart resulted in fundamental changes in the levels of key regulatory genes and myocyte differentiation\u2013specific genes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>These results indicate that GATA-6 is both necessary and sufficient for regulating the cardiac hypertrophic response and differentiated gene expression, both alone and in coordination with GATA-4.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.110.220764","type":"journal-article","created":{"date-parts":[[2010,8,13]],"date-time":"2010-08-13T02:50:59Z","timestamp":1281667859000},"page":"1032-1040","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":98,"title":["The Transcription Factor GATA-6 Regulates Pathological Cardiac Hypertrophy"],"prefix":"10.1161","volume":"107","author":[{"given":"Jop H.","family":"van Berlo","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Elrod","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten M.G.","family":"van den Hoogenhof","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen J.","family":"York","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Aronow","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Duncan","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.H.v.B., J.W.E., M.M.G.v.d.H., A.J.Y., B.J.A., J.D.M.); and the Howard Hughes Medical Institute (J.D.M.), University of Cincinnati, Cincinnati Children's Hospital Medical Center, Ohio; and Department of Cell Biology, Neurobiology and Anatomy (S.A.D.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000039105.49749.6f"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.391"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.915701"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.21.7460-7469.2001"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004240100699"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.5.730"},{"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":"10.1073\/pnas.0604604103"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R000029200"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2006.11.012"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.03.025"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102174200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32573"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000215985.18538.c4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401833101"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602543103"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-6-19"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000065442.64694.9f"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.4.723"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.53.38004"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvh077"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0775"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703173200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.3.272"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.17.6591"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02308"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.03.013"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.6.4355"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23769"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.110.220764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:41:27Z","timestamp":1715571687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.110.220764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,15]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,10,15]]}},"alternative-id":["10.1161\/CIRCRESAHA.110.220764"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.110.220764","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,15]]},"assertion":[{"value":"2010-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-08-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-08-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}