{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:50:06Z","timestamp":1772164206907,"version":"3.50.1"},"reference-count":37,"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":[[2012,6,15]]},"abstract":"<jats:p>\n                    Cardiomyocytes from failing hearts exhibit reduced levels of the sarcoplasmic reticulum (SR) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -ATPase (SERCA) and\/or increased activity of the endogenous SERCA inhibitor phospholamban. The resulting reduction in the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    affinity of SERCA impairs SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    cycling in this condition. We have previously investigated the physiological impact of increasing the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    affinity of SERCA by substituting SERCA2a with the higher affinity SERCA2b pump. When phospholamban was also ablated, these double knockouts (DKO) exhibited a dramatic reduction in total SERCA levels, severe hypertrophy, and diastolic dysfunction. We presently examined the role of cardiomyocyte Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis in both functional and structural remodeling in these hearts. Despite the low SERCA levels in DKO, we observed near-normal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis with rapid Ca\n                    <jats:sup>2+<\/jats:sup>\n                    reuptake even at high Ca\n                    <jats:sup>2+<\/jats:sup>\n                    loads and stimulation frequencies. Well-preserved global Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis in DKO was paradoxically associated with marked activation of the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent nuclear factor of activated T-cell-calcineurin pathway known to trigger hypertrophy. No activation of the MAP kinase signaling pathway was detected. These findings suggest that local changes in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis may play an important signaling role in DKO, perhaps due to reduced microdomain Ca\n                    <jats:sup>2+<\/jats:sup>\n                    buffering by SERCA2b. Furthermore, alterations in global Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis can also not explain impaired in vivo diastolic function in DKO. Taken together, our results suggest that normalizing global cardiomyocyte Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis does not necessarily protect against hypertrophy and heart failure development and that excessively increasing SERCA Ca\n                    <jats:sup>2+<\/jats:sup>\n                    affinity may be detrimental.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.01166.2011","type":"journal-article","created":{"date-parts":[[2012,4,14]],"date-time":"2012-04-14T00:50:01Z","timestamp":1334364601000},"page":"H2574-H2582","source":"Crossref","is-referenced-by-count":10,"title":["Phospholamban ablation in hearts expressing the high affinity SERCA2b isoform normalizes global Ca\n                    <sup>2+<\/sup>\n                    homeostasis but not Ca\n                    <sup>2+<\/sup>\n                    -dependent hypertrophic signaling"],"prefix":"10.1152","volume":"302","author":[{"given":"William E.","family":"Louch","sequence":"first","affiliation":[{"name":"Laboratory for Experimental Cardiology, University of Leuven, Leuven, Belgium;"},{"name":"Institute for Experimental Medical Research; Oslo University Hospital Ulevaal and University of Oslo, Oslo, Norway;"},{"name":"KG Jebsen Cardiac Research Center and Center for Heart Failure Research; University of Oslo, Oslo, Norway; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vangheluwe","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Transport Systems; University of Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginie","family":"Bito","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University of Leuven, Leuven, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Raeymaekers","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Transport Systems; University of Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Wuytack","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Transport Systems; University of Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin R.","family":"Sipido","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University of Leuven, Leuven, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.202663"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.03.013"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.025619"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000069032.81501.98"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.11.012"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235594"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.6.889"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/hc3601.095574"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306784200"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.260501097"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17892"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119544"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.185611"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2009.01.013"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118446"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2008.44.7.1221662"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.11.048"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-009-9216-8"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.183517"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.3.401"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1151"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81662-1"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.210740"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316738"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050808"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00126-X"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.05.014"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/hh2101.098466"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.121"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.1.C391"},{"key":"B31","first-page":"976","volume":"119","author":"Wu X","year":"2009","journal-title":"J Clin Invest"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.12.e61"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0834"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.14.10538"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.207423"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.05.013"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.20.14985"}],"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.01166.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T18:14:45Z","timestamp":1567966485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.01166.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,15]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,6,15]]}},"alternative-id":["10.1152\/ajpheart.01166.2011"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.01166.2011","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718352775.793493859","asserted-by":"object"}]},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,15]]}}}