{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:03:45Z","timestamp":1791291825426,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T00:00:00Z","timestamp":1315353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cytosolic calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>) is key for the regulation of many cellular processes, such cell signaling and proliferation, metabolism, and muscle contraction. In cardiomyocytes, Ca<jats:sup>2+<\/jats:sup>is an important regulator in many cellular functions such electrophysiological processes, excitation\u2010contraction coupling, regulation of contractile proteins activity, energy metabolism, cell death, and transcriptional regulation by the activation of Ca<jats:sup>2+<\/jats:sup>\u2010dependent transcriptional pathways. In cardiomyocytes, the two main Ca<jats:sup>2+<\/jats:sup>\u2010dependent pathways are the Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010calcineurin\u2010NFAT and the Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent kinases\u2010MEF2. Both pathways are involved in the transcriptional control of many cardiac genes. Cardiac hypertrophy (CH) and heart failure (HF) are characterized by alterations in calcium handling such a low sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>content, decreased rate of Ca<jats:sup>2+<\/jats:sup>removal from the sarcoplasm, increased diastolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>, and decreased systolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>, all of them contributing to diminished contractibility and force generation in failing heart. At gene expression level, there are also many changes such decreased levels of SERCA2a and activation of a fetal gene expression program in cardiomyocytes. A variety of Ca<jats:sup>2+<\/jats:sup>\u2010dependent signaling pathways have been implicated in CH and HF, but whether these pathways are interrelated and whether there is specificity among them are still unclear and under investigation. The focus of this review is to make an analysis of the current knowledge about the role of Ca<jats:sup>2+<\/jats:sup>signaling pathways in the regulation of cardiac gene expression making special emphasis in novel strategies to correct Ca<jats:sup>2+<\/jats:sup>handling alterations by means of SERCA2a gene therapy. \u00a9 2011 IUBMB IUBMB Life, 2011.<\/jats:p>","DOI":"10.1002\/iub.545","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T13:20:00Z","timestamp":1315401600000},"page":"847-855","source":"Crossref","is-referenced-by-count":50,"title":["Calcium\u2010regulated transcriptional pathways in the normal and pathologic heart"],"prefix":"10.1002","volume":"63","author":[{"given":"Angel","family":"Zarain\u2010Herzberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Fragoso\u2010Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Estrada\u2010Avil\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,9,7]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/415198a"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100455"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00925961"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00841.2010"},{"issue":"4","key":"e_1_2_8_6_2","first-page":"S18","article-title":"[Function and role of the sarcoplasmic reticulum in heart disease]","volume":"76","author":"Reyes\u2010Juarez J. L.","year":"2006","journal-title":"Arch. Cardiol. Mex."},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1139\/y06-023"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00274.2002"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-6363(96)00103-4"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.3.H744"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.2.179"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000145161.48545.B3"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.74.5.991"},{"issue":"1","key":"e_1_2_8_14_2","doi-asserted-by":"crossref","first-page":"I136","DOI":"10.1007\/s003950200042","article-title":"Targeting Ca2+ cycling proteins and the action potential in heart failure by gene transfer","volume":"97","author":"Kaprielian R.","year":"2002","journal-title":"Basic Res. Cardiol."},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.08.016"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.06.070"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.suppl_4.IV-14"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000194329.41863.89"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.982298"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr025"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-010-0092-0"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.03.006"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/147323000703500609"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00152.2009"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.3.865-878.2005"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712316105"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)02031-X"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.14.1.167"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfp165"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.608968"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.000539"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01611-07"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301646200"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707083200"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.194035"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8551"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80027-5"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00980.2009"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.05.014"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1159\/000099063"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608791103"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01222-08"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2126"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.102574"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.01.008"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.108.816686"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1247\/csf.07044"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.14.5096-5106.2000"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107146200"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709776200"},{"key":"e_1_2_8_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.04.005"},{"key":"e_1_2_8_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2008.05094.x"},{"key":"e_1_2_8_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707788200"},{"key":"e_1_2_8_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn357"},{"key":"e_1_2_8_55_2","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1096\/fasebj.10.11.8836044","article-title":"Modification of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomoxir","volume":"10","author":"Zarain\u2010Herzberg A.","year":"1996","journal-title":"FASEB, J."},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.11.3.345"},{"key":"e_1_2_8_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-005-9474-z"},{"key":"e_1_2_8_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.793"},{"key":"e_1_2_8_59_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.109.891184"},{"key":"e_1_2_8_60_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14712\/fb2010056010001","article-title":"Right ventricular beneficial effects of intracoronary SERCA2a gene transfer in an experimental model of heart failure","volume":"56","author":"Molina E. J.","year":"2010","journal-title":"Folia Biol. (Praha)"},{"key":"e_1_2_8_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq234"},{"key":"e_1_2_8_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301614"},{"key":"e_1_2_8_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2008.02.005"},{"key":"e_1_2_8_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2009.01.013"},{"key":"e_1_2_8_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.210757"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fiub.545","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.545","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T22:56:38Z","timestamp":1741560998000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,7]]},"references-count":64,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,10]]}},"alternative-id":["10.1002\/iub.545"],"URL":"https:\/\/doi.org\/10.1002\/iub.545","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,7]]}}}