{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:51:19Z","timestamp":1777506679194,"version":"3.51.4"},"reference-count":19,"publisher":"American Physiological Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:p> Pressure overload is known to be a cause of cardiac hypertrophy that often transits to heart failure. Although nuclear factor (NF)-\u03baB is a key factor in the progression of cardiac hypertrophy, its pathophysiology is yet to be elucidated. Thus, we aimed to show that inhibition of NF-\u03baB activation improves pressure overload-induced cardiac dysfunction. To assess the effect of inhibition on NF-\u03baB activation in pressure overload cardiac hypertrophy, we used IMD-1041 in a murine thoracic aortic constriction (TAC) model. IMD-1041 inhibits the phosphorylation of I\u03baB via inhibition of I\u03baB kinase-\u03b2. IMD-1041 (100 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) or vehicle was administered orally into mice once a day, and mice were euthanized on day 42 after TAC. TAC resulted in left ventricular wall thickening, cardiac dysfunction, and increases of heart and lung weight, whereas IMD-1041 significantly suppressed the development of cardiac hypertropy 6 wk after TAC. Histologically, developed cardiac fibrosis and cardiomyocyte hypertrophy occurred in the vehicle-treated group, whereas IMD-1041 significantly attenuated these changes. IMD-1041 suppressed the expression of p65-positive cells and nuclear translocation of p65 induced by TAC compared with vehicle. Matrix metalloproteinase-2 activity increased in the vehicle + TAC-treated group; however, it was suppressed in the IMD-1041 + TAC-treated group. IMD-1041 treatment from day 28 to day 42 after TAC significantly attenuated the decrease in the percentage of fractional shortening and cardiac fibrosis without an antihypertrophic effect. In conclusion, IMD-1041 may be useful for preventing pressure overload-induced cardiac dysfunction and the transition of cardiac hypertrophy to contraction failure via suppression of NF-\u03baB activation. <\/jats:p>","DOI":"10.1152\/ajpheart.00290.2012","type":"journal-article","created":{"date-parts":[[2012,10,6]],"date-time":"2012-10-06T01:41:46Z","timestamp":1349487706000},"page":"H1435-H1445","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of I\u03baB phosphorylation prevents load-induced cardiac dysfunction in mice"],"prefix":"10.1152","volume":"303","author":[{"given":"Tetsu","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahito","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Tokya, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-ichi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Tokya, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asuka","family":"Sekinishi","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Itai","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Molecular Design, Tokyo, Japan; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunobu","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Tokya, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuaki","family":"Isobe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43569"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00434-5"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00723-X"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-010-0373-1"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.10.006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.193318"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00108.2003"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nri910"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00124.2004"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000208840.30778.00"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103166200"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00549.2006"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.04.031"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.10.006"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.07.009"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40295"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01377-8"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.09.002"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405844200"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00290.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T17:35:58Z","timestamp":1567964158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00290.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,15]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12,15]]}},"alternative-id":["10.1152\/ajpheart.00290.2012"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00290.2012","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,15]]}}}