{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T19:25:33Z","timestamp":1770146733665,"version":"3.49.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,12,18]],"date-time":"2009-12-18T00:00:00Z","timestamp":1261094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The transcription factor MEF2 is a downstream target for several hypertrophic signalling pathways in the heart, suggesting that MEF2 may act as a valuable therapeutic target in the treatment of heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this study, we investigated the potential benefits of overall MEF2 inhibition in a mouse model of chronic pressure overloading, by subjecting transgenic mice expressing a dominant negative form of MEF2 (DN-MEF2 Tg) in the heart, to transverse aortic constriction (TAC). Histological analysis revealed no major differences in cardiac remodelling between DN-MEF2 Tg and control mice after TAC. Surprisingly, echocardiographic analysis revealed that DN-MEF2 Tg mice had a decrease in cardiac function compared with control animals. Analysis of the mitochondrial respiratory chain showed that DN-MEF2 Tg mice displayed lower expression of NADH dehydrogenase subunit 6 (ND6), part of mitochondrial Complex I. The reduced expression of ND6 in DN-MEF2 Tg mice after pressure overload correlated with an increase in cell death secondary to overproduction of reactive oxygen species (ROS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data suggest that MEF2 transcriptional activity is required for mitochondrial function and its inhibition predisposes the heart to impaired mitochondrial function, overproduction of ROS, enhanced cell death, and cardiac dysfunction, following pressure overload.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfp165","type":"journal-article","created":{"date-parts":[[2009,12,18]],"date-time":"2009-12-18T13:19:49Z","timestamp":1261142389000},"page":"4-12","source":"Crossref","is-referenced-by-count":25,"title":["MEF2 Transcriptional Activity Maintains Mitochondrial Adaptation in Cardiac Pressure Overload"],"prefix":"10.1093","volume":"12","author":[{"given":"Hamid","family":"el Azzouzi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Cardiovascular Research Institute Maastricht, Maastricht University , Maastricht ,","place":["The Netherlands"]},{"name":"The Hubrecht Institute and Interuniversity Cardiology Institute Netherlands, Royal Netherlands Academy of Sciences , Utrecht ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph J.","family":"van Oort","sequence":"additional","affiliation":[{"name":"The Hubrecht Institute and Interuniversity Cardiology Institute Netherlands, Royal Netherlands Academy of Sciences , Utrecht ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel","family":"van der Nagel","sequence":"additional","affiliation":[{"name":"The Hubrecht Institute and Interuniversity Cardiology Institute Netherlands, Royal Netherlands Academy of Sciences , Utrecht ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim","family":"Sluiter","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Erasmus MC , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin W.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Franz Volhard Klinik, Max Delbr\u00fcck Center for Molecular Medicine , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon J.","family":"De Windt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Cardiovascular Research Institute Maastricht, Maastricht University , Maastricht ,","place":["The Netherlands"]},{"name":"The Hubrecht Institute and 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