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We therefore investigated the expression of genes coding for major inward and outward ion channels, calcium binding proteins, ion receptors, ion exchangers, calcium ATPases, and calcium\/calmodulin\u2010dependent protein kinases in explanted hearts (\n                    <jats:italic>n<\/jats:italic>\n                    =13) of patients diagnosed with end\u2010stage heart failure. With the exception of Kv11.1 and Kir3.1 and when compared with healthy controls, major sodium, potassium, and calcium ion channels, ion transporters, and exchangers were significantly repressed, but expression of Kv7.1, HCN4, troponin C and I, SERCA1, and phospholamban was elevated. Hierarchical gene cluster analysis provided novel insight into regulated gene networks. Significant induction of the transcriptional repressor m\u2010Bop and the translational repressor NAT1 coincided with repressed cardiac gene expression. The statistically significant negative correlation between repressors and ion channels points to a mechanism of disease. We observed coregulation of ion channels and the androgen receptor and propose a role for this receptor in ion channel regulation. Overall, the reversal of repressed ion channel gene expression in patients with implanted assist devices exemplifies the complex interactions between pressure load\/stretch force and heart\u2010specific gene expression.\u2014Borlak, J., Thum, T. Hallmarks of ion channel gene expression in end\u2010stage heart failure.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    17, 1592\u20131608 (2003)\n                  <\/jats:p>","DOI":"10.1096\/fj.02-0889com","type":"journal-article","created":{"date-parts":[[2003,9,4]],"date-time":"2003-09-04T14:58:00Z","timestamp":1062687480000},"page":"1592-1608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["Hallmarks of ion channel gene expression in end\u2010stage heart failure"],"prefix":"10.1096","volume":"17","author":[{"given":"J\u00fcrgen","family":"Borlak","sequence":"first","affiliation":[{"name":"Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology  30625 Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology  30625 Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1067\/mhj.2000.111112","article-title":"Left ventricular hypertrophy as a predictor of coronary heart disease mortality and the effect of hypertension","volume":"14","author":"Brown D. 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