{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:24:52Z","timestamp":1785363892304,"version":"3.55.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T00:00:00Z","timestamp":1540252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T00:00:00Z","timestamp":1540252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health &amp; Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["HL097357"],"award-info":[{"award-number":["HL097357"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health &amp; Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["HL137220"],"award-info":[{"award-number":["HL137220"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The adipokine resistin has been proposed to link obesity, insulin resistance and diabetes. We have previously reported that diabetic hearts express high levels of resistin while overexpression of resistin in adult rat hearts gives rise to a phenotype resembling diabetic cardiomyopathy. The transcriptional regulation of resistin in diabetic cardiac tissue is currently unknown. This study investigated the mechanism of resistin upregulation and the role of Serca2a in its transcriptional suppression. We demonstrate that restoration of Ca<jats:sup>2+<\/jats:sup> homeostasis in diabetic hearts, through normalization of Serca2a function genetically and pharmacologically, suppressed resistin expression via inhibition of NFATc. H9c2 myocytes stimulated with high-glucose concentration or Ca<jats:sup>2+<\/jats:sup> time-dependently increased NFATc and resistin expression while addition of the Ca<jats:sup>2+<\/jats:sup> chelator BAPTA-AM attenuated this effect. NFATc expression was enhanced in hearts from <jats:italic>ob\/ob<\/jats:italic> diabetic and from cardiac-specific Serca2a<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Similarly, NFATc increased resistin expression in myocytes cultured in low glucose while the NFATc inhibitor VIVIT blocked glucose-induced resistin expression, suggesting that hyperglycemia\/diabetes induces resistin expression possibly through NFATc activation. Interestingly, overexpression of Serca2a or VIVIT mitigated glucose-stimulated resistin and NFATc expression and enhanced AMPK activity, a downstream target of resistin signaling. NFATc direct activation of resistin was verified by resistin promoter luciferase activity and chromatin-immunoprecipitation analysis. Interestingly, activation of Serca2a by a novel agonist, CDN1163, mirrored the effects of AAV9-Serca2a gene transfer on resistin expression and its promoter activity and AMPK signaling in diabetic mice. These findings parse a role for Ca<jats:sup>2+<\/jats:sup> in resistin transactivation and provide support that manipulation of Serca2a-NFATc-Resistin axis might be useful in hyper-resistinemic conditions.<\/jats:p>","DOI":"10.1038\/s41598-018-34112-4","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T11:30:19Z","timestamp":1539775819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A role for calcium in resistin transcriptional activation in diabetic hearts"],"prefix":"10.1038","volume":"8","author":[{"given":"Rajvir","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.","family":"Hajjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-2923","authenticated-orcid":false,"given":"Djamel","family":"Lebeche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,23]]},"reference":[{"key":"34112_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1152\/physrev.00017.2007","volume":"88","author":"ED Abel","year":"2008","unstructured":"Abel, E. D., Litwin, S. E. & Sweeney, G. Cardiac remodeling in obesity. Physiological reviews 88, 389\u2013419 (2008).","journal-title":"Physiological reviews"},{"key":"34112_CR2","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1161\/01.CIR.0000060923.07573.F2","volume":"107","author":"J Steinberger","year":"2003","unstructured":"Steinberger, J. & Daniels, S. R. Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 107, 1448\u20131453 (2003).","journal-title":"Circulation"},{"key":"34112_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0728-6","volume":"17","author":"TR Einarson","year":"2018","unstructured":"Einarson, T. R., Acs, A., Ludwig, C. & Panton, U. H. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007\u20132017. Cardiovascular diabetology 17, 83 (2018).","journal-title":"Cardiovascular diabetology"},{"key":"34112_CR4","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1253\/circj.CJ-13-1564","volume":"78","author":"YK Bando","year":"2014","unstructured":"Bando, Y. K. & Murohara, T. Diabetes-related heart failure. Circ J 78, 576\u2013583 (2014).","journal-title":"Circ J"},{"key":"34112_CR5","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1161\/CIRCRESAHA.117.311586","volume":"122","author":"G Jia","year":"2018","unstructured":"Jia, G., Hill, M. A. & Sowers, J. R. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circ Res 122, 624\u2013638 (2018).","journal-title":"Circ Res"},{"key":"34112_CR6","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1161\/CIRCULATIONAHA.106.679597","volume":"115","author":"S Boudina","year":"2007","unstructured":"Boudina, S. & Abel, E. D. Diabetic cardiomyopathy revisited. Circulation 115, 3213\u20133223 (2007).","journal-title":"Circulation"},{"key":"34112_CR7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1586\/erc.10.17","volume":"8","author":"JS Dobrin","year":"2010","unstructured":"Dobrin, J. S. & Lebeche, D. Diabetic cardiomyopathy: signaling defects and therapeutic approaches. Expert Rev Cardiovasc Ther 8, 373\u2013391 (2010).","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"34112_CR8","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1210\/er.2003-0012","volume":"25","author":"ZY Fang","year":"2004","unstructured":"Fang, Z. Y., Prins, J. B. & Marwick, T. H. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocrine reviews 25, 543\u2013567 (2004).","journal-title":"Endocrine reviews"},{"key":"34112_CR9","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1161\/01.RES.0000207406.94146.c2","volume":"98","author":"IG Poornima","year":"2006","unstructured":"Poornima, I. G., Parikh, P. & Shannon, R. P. Diabetic cardiomyopathy: the search for a unifying hypothesis. Circ Res 98, 596\u2013605 (2006).","journal-title":"Circ Res"},{"key":"34112_CR10","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.tcm.2007.09.005","volume":"17","author":"O Gualillo","year":"2007","unstructured":"Gualillo, O., Gonzalez-Juanatey, J. R. & Lago, F. The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. Trends Cardiovasc Med 17, 275\u2013283 (2007).","journal-title":"Trends Cardiovasc Med"},{"key":"34112_CR11","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1055\/s-2007-985897","volume":"39","author":"MA Lazar","year":"2007","unstructured":"Lazar, M. A. Resistin- and Obesity-associated metabolic diseases. Horm Metab Res 39, 710\u2013716 (2007).","journal-title":"Horm Metab Res"},{"key":"34112_CR12","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/35053000","volume":"409","author":"CM Steppan","year":"2001","unstructured":"Steppan, C. M. et al. The hormone resistin links obesity to diabetes. Nature 409, 307\u2013312 (2001).","journal-title":"Nature"},{"key":"34112_CR13","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1210\/en.2004-0985","volume":"146","author":"N Sato","year":"2005","unstructured":"Sato, N. et al. Adenovirus-mediated high expression of resistin causes dyslipidemia in mice. Endocrinology 146, 273\u2013279, https:\/\/doi.org\/10.1210\/en.2004-0985 (2005).","journal-title":"Endocrinology"},{"key":"34112_CR14","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1172\/jci20785","volume":"114","author":"H Satoh","year":"2004","unstructured":"Satoh, H. et al. Adenovirus-mediated chronic \u201chyper-resistinemia\u201d leads to in vivo insulin resistance in normal rats. The Journal of clinical investigation 114, 224\u2013231, https:\/\/doi.org\/10.1172\/jci20785 (2004).","journal-title":"The Journal of clinical investigation"},{"key":"34112_CR15","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1210\/me.2002-0048","volume":"16","author":"MW Rajala","year":"2002","unstructured":"Rajala, M. W. et al. Cell type-specific expression and coregulation of murine resistin and resistin-like molecule-alpha in adipose tissue. Mol Endocrinol 16, 1920\u20131930 (2002).","journal-title":"Mol Endocrinol"},{"key":"34112_CR16","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1126\/science.1092341","volume":"303","author":"RR Banerjee","year":"2004","unstructured":"Banerjee, R. R. et al. Regulation of fasted blood glucose by resistin. Science New York, N.Y 303, 1195\u20131198 (2004).","journal-title":"Science New York, N.Y"},{"key":"34112_CR17","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.2337\/db05-0615","volume":"55","author":"Y Qi","year":"2006","unstructured":"Qi, Y. et al. Loss of resistin improves glucose homeostasis in leptin deficiency. Diabetes 55, 3083\u20133090 (2006).","journal-title":"Diabetes"},{"key":"34112_CR18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0378-1119(02)01213-1","volume":"305","author":"S Ghosh","year":"2003","unstructured":"Ghosh, S., Singh, A. K., Aruna, B., Mukhopadhyay, S. & Ehtesham, N. Z. The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications. Gene 305, 27\u201334 (2003).","journal-title":"Gene"},{"key":"34112_CR19","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1038\/oby.2005.215","volume":"13","author":"T Pischon","year":"2005","unstructured":"Pischon, T. et al. Association of plasma resistin levels with coronary heart disease in women. Obesity research 13, 1764\u20131771 (2005).","journal-title":"Obesity research"},{"key":"34112_CR20","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.jacc.2008.07.073","volume":"53","author":"DS Frankel","year":"2009","unstructured":"Frankel, D. S. et al. Resistin, adiponectin, and risk of heart failure the Framingham offspring study. J Am Coll Cardiol 53, 754\u2013762 (2009).","journal-title":"J Am Coll Cardiol"},{"key":"34112_CR21","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/sj.ijo.0802625","volume":"28","author":"M Bajaj","year":"2004","unstructured":"Bajaj, M., Suraamornkul, S., Hardies, L. J., Pratipanawatr, T. & DeFronzo, R. A. Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients. Int J Obes Relat Metab Disord 28, 783\u2013789 (2004).","journal-title":"Int J Obes Relat Metab Disord"},{"key":"34112_CR22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1210\/jc.2005-1653","volume":"91","author":"MS Burnett","year":"2006","unstructured":"Burnett, M. S., Devaney, J. M., Adenika, R. J., Lindsay, R. & Howard, B. V. Cross-sectional associations of resistin, coronary heart disease, and insulin resistance. J Clin Endocrinol Metab 91, 64\u201368 (2006).","journal-title":"J Clin Endocrinol Metab"},{"key":"34112_CR23","doi-asserted-by":"publisher","first-page":"6098","DOI":"10.1210\/jc.2003-030898","volume":"88","author":"PG McTernan","year":"2003","unstructured":"McTernan, P. G. et al. Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 88, 6098\u20136106 (2003).","journal-title":"J Clin Endocrinol Metab"},{"key":"34112_CR24","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1253\/circj.71.460","volume":"71","author":"Y Takeishi","year":"2007","unstructured":"Takeishi, Y. et al. Serum resistin is associated with high risk in patients with congestive heart failure\u2013a novel link between metabolic signals and heart failure. Circ J 71, 460\u2013464 (2007).","journal-title":"Circ J"},{"key":"34112_CR25","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1136\/pgmj.2010.113571","volume":"87","author":"TE Korah","year":"2011","unstructured":"Korah, T. E., Ibrahim, H. H., Badr, E. A. E. & ElShafie, M. K. Serum resistin in acute myocardial infarction patients with and without diabetes mellitus. Postgraduate Medical Journal 87, 463\u2013467 (2011).","journal-title":"Postgraduate Medical Journal"},{"key":"34112_CR26","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1161\/01.CIR.0000155620.10387.43","volume":"111","author":"MP Reilly","year":"2005","unstructured":"Reilly, M. P. et al. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111, 932\u2013939 (2005).","journal-title":"Circulation"},{"key":"34112_CR27","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.yjmcc.2008.05.006","volume":"45","author":"M Kim","year":"2008","unstructured":"Kim, M. et al. Role of resistin in cardiac contractility and hypertrophy. J Mol Cell Cardiol 45, 270\u2013280 (2008).","journal-title":"J Mol Cell Cardiol"},{"key":"34112_CR28","doi-asserted-by":"publisher","first-page":"18465","DOI":"10.1074\/jbc.M110.200022","volume":"286","author":"S Kang","year":"2011","unstructured":"Kang, S., Chemaly, E. R., Hajjar, R. J. & Lebeche, D. Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase\/mammalian target of rapamycin (AMPK\/mTOR) and c-Jun N-terminal kinase\/insulin receptor substrate 1 (JNK\/IRS1) pathways. J Biol Chem 286, 18465\u201318473 (2011).","journal-title":"J Biol Chem"},{"key":"34112_CR29","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.yjmcc.2011.04.006","volume":"51","author":"ER Chemaly","year":"2011","unstructured":"Chemaly, E. R. et al. Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats. J Mol Cell Cardiol 51, 144\u2013155 (2011).","journal-title":"J Mol Cell Cardiol"},{"key":"34112_CR30","doi-asserted-by":"publisher","first-page":"5185","DOI":"10.1074\/jbc.M115.705012","volume":"291","author":"S Kang","year":"2016","unstructured":"Kang, S. et al. Small Molecular Allosteric Activator of the Sarco\/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Attenuates Diabetes and Metabolic Disorders. J Biol Chem 291, 5185\u20135198 (2016).","journal-title":"J Biol Chem"},{"key":"34112_CR31","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.ymthe.2006.01.002","volume":"13","author":"S Sakata","year":"2006","unstructured":"Sakata, S. et al. Mechanical and metabolic rescue in a type II diabetes model of cardiomyopathy by targeted gene transfer. Mol Ther 13, 987\u2013996 (2006).","journal-title":"Mol Ther"},{"issue":"3","key":"34112_CR32","doi-asserted-by":"publisher","first-page":"H1137","DOI":"10.1152\/ajpheart.2001.281.3.H1137","volume":"281","author":"Yan Zhong","year":"2001","unstructured":"Zhong, Y., Ahmed, S., Grupp, I. L. & Matlib, M. A. Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts. Am J Physiol Heart Circ Physiol 281 (2001).","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"34112_CR33","doi-asserted-by":"publisher","first-page":"7372","DOI":"10.1128\/MCB.00580-06","volume":"26","author":"TT Yang","year":"2006","unstructured":"Yang, T. T. et al. Role of transcription factor NFAT in glucose and insulin homeostasis. Mol Cell Biol 26, 7372\u20137387 (2006).","journal-title":"Mol Cell Biol"},{"key":"34112_CR34","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1161\/CIRCRESAHA.109.194035","volume":"105","author":"SM MacDonnell","year":"2009","unstructured":"MacDonnell, S. M. et al. CaMKII negatively regulates calcineurin-NFAT signaling in cardiac myocytes. Circ Res 105, 316\u2013325 (2009).","journal-title":"Circ Res"},{"key":"34112_CR35","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.yjmcc.2007.08.009","volume":"43","author":"J Gao","year":"2007","unstructured":"Gao, J. et al. Resistin, an adipocytokine, offers protection against acute myocardial infarction. J Mol Cell Cardiol 43, 601\u2013609 (2007).","journal-title":"J Mol Cell Cardiol"},{"key":"34112_CR36","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.bbrc.2006.08.052","volume":"349","author":"SE Rothwell","year":"2006","unstructured":"Rothwell, S. E., Richards, A. M. & Pemberton, C. J. Resistin worsens cardiac ischaemia-reperfusion injury. Biochem Biophys Res Commun 349, 400\u2013407 (2006).","journal-title":"Biochem Biophys Res Commun"},{"key":"34112_CR37","doi-asserted-by":"publisher","first-page":"5337","DOI":"10.1113\/jphysiol.2013.258731","volume":"591","author":"ER Chemaly","year":"2013","unstructured":"Chemaly, E. R. et al. Differential patterns of replacement and reactive fibrosis in pressure and volume overload are related to the propensity for ischaemia and involve resistin. J Physiol 591, 5337\u20135355 (2013).","journal-title":"J Physiol"},{"key":"34112_CR38","doi-asserted-by":"publisher","first-page":"19754","DOI":"10.1074\/jbc.M201451200","volume":"277","author":"HB Hartman","year":"2002","unstructured":"Hartman, H. B., Hu, X., Tyler, K. X., Dalal, C. K. & Lazar, M. A. Mechanisms regulating adipocyte expression of resistin. J Biol Chem 277, 19754\u201319761 (2002).","journal-title":"J Biol Chem"},{"key":"34112_CR39","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1210\/me.2011-1181","volume":"26","author":"T Kono","year":"2012","unstructured":"Kono, T. et al. PPAR-gamma activation restores pancreatic islet SERCA2 levels and prevents beta-cell dysfunction under conditions of hyperglycemic and cytokine stress. Mol Endocrinol 26, 257\u2013271 (2012).","journal-title":"Mol Endocrinol"},{"issue":"10","key":"34112_CR40","doi-asserted-by":"publisher","first-page":"e81379","DOI":"10.1371\/journal.pone.0081379","volume":"8","author":"Yaqin Chen","year":"2013","unstructured":"Chen, Y., Chen, M., Wu, Z. & Zhao, S. Ox-LDL induces ER stress and promotes the adipokines secretion in 3T3-L1 adipocytes. PLoS One 8 (2013).","journal-title":"PLoS ONE"},{"key":"34112_CR41","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/jdi.12434","volume":"7","author":"J Hamada","year":"2016","unstructured":"Hamada, J. et al. Endoplasmic reticulum stress induced by tunicamycin increases resistin messenger ribonucleic acid through the pancreatic endoplasmic reticulum eukaryotic initiation factor 2alpha kinase-activating transcription factor 4-CAAT\/enhancer binding protein-alpha homologous protein pathway in THP-1 human monocytes. J Diabetes Investig 7, 312\u2013323 (2016).","journal-title":"J Diabetes Investig"},{"key":"34112_CR42","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.2337\/db08-1706","volume":"58","author":"MI Lefterova","year":"2009","unstructured":"Lefterova, M. I. et al. Endoplasmic reticulum stress regulates adipocyte resistin expression. Diabetes 58, 1879\u20131886 (2009).","journal-title":"Diabetes"},{"key":"34112_CR43","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0092-8674(00)81573-1","volume":"93","author":"JD Molkentin","year":"1998","unstructured":"Molkentin, J. D. et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93, 215\u2013228 (1998).","journal-title":"Cell"},{"key":"34112_CR44","doi-asserted-by":"publisher","first-page":"3524","DOI":"10.1074\/jbc.M004275200","volume":"276","author":"M Ichida","year":"2001","unstructured":"Ichida, M. & Finkel, T. Ras regulates NFAT3 activity in cardiac myocytes. J Biol Chem 276, 3524\u20133530 (2001).","journal-title":"J Biol Chem"},{"issue":"6","key":"34112_CR45","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nm0698-661","volume":"4","author":"Seigo Izumo","year":"1998","unstructured":"Izumo, S. & Aoki, H. Calcineurin\u2013the missing link in cardiac hypertrophy. (Nat Med. 1998 Jun; 4(6):661-2.).","journal-title":"Nature Medicine"},{"key":"34112_CR46","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1161\/01.RES.84.6.623","volume":"84","author":"EN Olson","year":"1999","unstructured":"Olson, E. N. & Molkentin, J. D. Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype? Circ Res 84, 623\u2013632 (1999).","journal-title":"Circ Res"},{"key":"34112_CR47","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/S0896-6273(00)80040-9","volume":"16","author":"S Finkbeiner","year":"1996","unstructured":"Finkbeiner, S. & Greenberg, M. E. Ca(2+)-dependent routes to Ras: mechanisms for neuronal survival, differentiation, and plasticity? Neuron 16, 233\u2013236 (1996).","journal-title":"Neuron"},{"key":"34112_CR48","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s11626-010-9368-1","volume":"47","author":"SJ Watkins","year":"2011","unstructured":"Watkins, S. J., Borthwick, G. M. & Arthur, H. M. The H9C2 cell line and primary neonatal cardiomyocyte cells show similar hypertrophic responses in vitro. In vitro cellular & developmental biology. Animal 47, 125\u2013131 (2011).","journal-title":"In vitro cellular & developmental biology. Animal"},{"key":"34112_CR49","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.bbamcr.2014.11.015","volume":"1853","author":"AV Kuznetsov","year":"2015","unstructured":"Kuznetsov, A. V., Javadov, S., Sickinger, S., Frotschnig, S. & Grimm, M. H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation. Biochimica et biophysica acta 1853, 276\u2013284 (2015).","journal-title":"Biochimica et biophysica acta"},{"key":"34112_CR50","doi-asserted-by":"publisher","first-page":"48617","DOI":"10.1074\/jbc.M206532200","volume":"277","author":"E van Rooij","year":"2002","unstructured":"van Rooij, E. et al. Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy. J Biol Chem 277, 48617\u201348626 (2002).","journal-title":"J Biol Chem"},{"key":"34112_CR51","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1161\/01.RES.0000069211.82346.46","volume":"92","author":"WT Pu","year":"2003","unstructured":"Pu, W. T., Ma, Q. & Izumo, S. NFAT transcription factors are critical survival factors that inhibit cardiomyocyte apoptosis during phenylephrine stimulation in vitro. Circ Res 92, 725\u2013731 (2003).","journal-title":"Circ Res"},{"key":"34112_CR52","doi-asserted-by":"publisher","first-page":"H2001","DOI":"10.1152\/ajpheart.01072.2009","volume":"298","author":"A Rinne","year":"2010","unstructured":"Rinne, A. et al. Isoform- and tissue-specific regulation of the Ca(2+)-sensitive transcription factor NFAT in cardiac myocytes and heart failure. Am J Physiol Heart Circ Physiol 298, H2001\u20132009 (2010).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"34112_CR53","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ceca.2017.07.001","volume":"69","author":"ER Chemaly","year":"2018","unstructured":"Chemaly, E. R., Troncone, L. & Lebeche, D. SERCA control of cell death and survival. Cell Calcium 69, 46\u201361 (2018).","journal-title":"Cell Calcium"},{"key":"34112_CR54","doi-asserted-by":"crossref","unstructured":"Hammoudi, N. & Lebeche, D. Calcium Signaling in Cardiovascular Physiology and Pathology. In Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Gowraganahalli Jagadeesh Pitchai Balakumar Khin Maung-U Editors (2015).","DOI":"10.1007\/978-3-319-15961-4_4"},{"key":"34112_CR55","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev.physiol.70.113006.100455","volume":"70","author":"DM Bers","year":"2008","unstructured":"Bers, D. M. Calcium cycling and signaling in cardiac myocytes. Annual review of physiology 70, 23\u201349 (2008).","journal-title":"Annual review of physiology"},{"key":"34112_CR56","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1161\/hc3601.095574","volume":"104","author":"F del Monte","year":"2001","unstructured":"del Monte, F. et al. Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure. Circulation 104, 1424\u20131429 (2001).","journal-title":"Circulation"},{"key":"34112_CR57","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ceca.2009.07.004","volume":"46","author":"KB Andersson","year":"2009","unstructured":"Andersson, K. B. et al. Mice carrying a conditional Serca2(flox) allele for the generation of Ca(2+) handling-deficient mouse models. Cell Calcium 46, 219\u2013225 (2009).","journal-title":"Cell Calcium"},{"key":"34112_CR58","doi-asserted-by":"publisher","first-page":"0006474","DOI":"10.1371\/journal.pone.0006474","volume":"4","author":"I Karakikes","year":"2009","unstructured":"Karakikes, I. et al. Gene remodeling in type 2 diabetic cardiomyopathy and its phenotypic rescue with SERCA2a. PLoS One 4, 0006474 (2009).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34112-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34112-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34112-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:45:12Z","timestamp":1671619512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34112-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,23]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["34112"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-34112-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,23]]},"assertion":[{"value":"25 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15633"}}