{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:51:29Z","timestamp":1789854689759,"version":"4.0.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"\n Background<\/jats:title>\n \n The expression of a novel cardiac glucose transporter,\n SGLT<\/jats:styled-content>\n 1, is increased in glycogen storage cardiomyopathy secondary to mutations in\n \n PRKAG<\/jats:styled-content>\n 2\n <\/jats:italic>\n . We sought to determine the role of\n SGLT<\/jats:styled-content>\n 1 in the pathogenesis of\n \n PRKAG<\/jats:styled-content>\n 2\n <\/jats:italic>\n cardiomyopathy and its role in cardiac structure and function.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Transgenic mice with cardiomyocyte\u2010specific overexpression of human T400N mutant\n PRKAG2<\/jats:italic>\n cDNA<\/jats:styled-content>\n (TG\n T400N<\/jats:sup>\n ) and transgenic mice with cardiomyocyte\u2010specific RNA interference knockdown of SGLT1 (TG\n SGLT1\u2010DOWN<\/jats:sup>\n ) were crossed to produce double\u2010transgenic mice (TG\n T400N<\/jats:sup>\n \/TG\n SGLT1\u2010DOWN<\/jats:sup>\n ). Tet\u2010off transgenic mice conditionally overexpressing cardiac SGLT1 in the absence of doxycycline were also constructed (TG\n SGLT\u2010ON<\/jats:sup>\n ). Relative to TG\n T400N<\/jats:sup>\n mice, TG\n T400N<\/jats:sup>\n \/TG\n SGLT1\u2010DOWN<\/jats:sup>\n mice exhibited decreases in cardiac SGLT1 expression (63% decrease,\n P<\/jats:italic>\n <0.05), heart\/body weight ratio, markers of cardiac hypertrophy, and cardiac glycogen content. TG\n T400N<\/jats:sup>\n \/TG\n SGLT1\u2010DOWN<\/jats:sup>\n mice had less left ventricular dilation at age 12\u00a0weeks compared to TG\n T400N<\/jats:sup>\n mice. Relative to wildtype (WT) mice, TG\n SGLT1\u2010ON<\/jats:sup>\n mice exhibited increases in heart\/body weight ratio, glycogen content, and markers of cardiac hypertrophy at ages 10 and 20\u00a0weeks. TG\n SGLT1\u2010ON<\/jats:sup>\n mice had increased myocyte size and interstitial fibrosis, and progressive left ventricular dysfunction. When SGLT1 was suppressed after 10\u00a0weeks of overexpression (TG\n SGLT1\u2010ON\/OFF<\/jats:sup>\n ), there was a reduction in cardiac hypertrophy and improvement in left ventricular failure.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Cardiac knockdown of\n SGLT<\/jats:styled-content>\n 1 in a murine model of\n \n PRKAG<\/jats:styled-content>\n 2\n <\/jats:italic>\n cardiomyopathy attenuates the disease phenotype, implicating\n SGLT<\/jats:styled-content>\n 1 in the pathogenesis. Overexpression of\n SGLT<\/jats:styled-content>\n 1 causes pathologic cardiac hypertrophy and left ventricular failure that is reversible. This is the first report of cardiomyocyte\u2010specific transgenic knockdown of a target gene.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.000899","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T02:01:45Z","timestamp":1407204105000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Transgenic Knockdown of Cardiac Sodium\/Glucose Cotransporter 1 (SGLT1) Attenuates\n PRKAG2<\/i>\n Cardiomyopathy, Whereas Transgenic Overexpression of Cardiac SGLT1 Causes Pathologic Hypertrophy and Dysfunction in Mice"],"prefix":"10.1161","volume":"3","author":[{"given":"Mohun","family":"Ramratnam","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine,\rDepartment of Medicine,\rUniversity of Wisconsin,\rMadison, WI"},{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"D'Auria","sequence":"additional","affiliation":[{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wang","sequence":"additional","affiliation":[{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Yin N.","family":"Huang","sequence":"additional","affiliation":[{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhaan","family":"Ahmad","sequence":"additional","affiliation":[{"name":"UPMC Heart and Vascular Institute and Division of Cardiology,\rDepartment of Medicine,\rUniversity of Pittsburgh,\rPittsburgh, PA"},{"name":"Department of Human Genetics,\rUniversity of Pittsburgh,\rPittsburgh, PA"},{"name":"Division of Cardiovascular Medicine,\rDepartment of Internal Medicine,\rUniversity of Iowa Carver College of Medicine,\rIowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(98)01340-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0982"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214571"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.06.067"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000075270.13497.2B"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000151291.32974.D5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01020.2005"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30658"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.12.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302364"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn116"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp190"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.06.003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.2979"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31568-0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002642"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000065442.64694.9F"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.550806"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7605"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.1.F10"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfp191"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.10.025"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr230"}],"container-title":["Journal of the American Heart 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