{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:15:19Z","timestamp":1793222119498,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>\n                      Atrial fibrillation is characterized by progressive atrial structural and electrical changes (atrial remodeling) that favor arrhythmia recurrence and maintenance. Reduction of L-type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      current (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Ca,L<\/jats:sub>\n                      ) density is a hallmark of the electrical remodeling. Alterations in atrial microRNAs could contribute to the protein changes underlying atrial fibrillation\u2013induced atrial electrical remodeling. This study was undertaken to compare miR-21 levels in isolated myocytes from atrial appendages obtained from patients in sinus rhythm and with chronic atrial fibrillation (CAF) and to determine whether L-type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channel subunits are targets for miR-21.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Quantitative polymerase chain reaction analysis showed that miR-21 was expressed in human atrial myocytes from patients in sinus rhythm and that its expression was significantly greater in CAF myocytes. There was an inverse correlation between miR-21 and the mRNA of the \u03b11c subunit of the calcium channel (CACNA1C) expression and\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Ca,L<\/jats:sub>\n                      density. Computational analyses predicted that CACNA1C and the mRNA of the \u03b22 subunit of the calcium channel (CACNB2) could be potential targets for miR-21. Luciferase reporter assays demonstrated that miR-21 produced a concentration-dependent decrease in the luciferase activity in Chinese Hamster Ovary cells transfected with CACNA1C and CACNB2 3\u2032 untranslated region regions. miR-21 transfection in HL-1 cells produced changes in\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Ca,L<\/jats:sub>\n                      properties qualitatively similar to those produced by CAF (ie, a marked reduction of\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Ca,L<\/jats:sub>\n                      density and shift of the inactivation curves to more depolarized potentials).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      Our results demonstrated that CAF increases miR-21 expression in enzymatically isolated human atrial myocytes. Moreover, it decreases\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Ca,L<\/jats:sub>\n                      density by downregulating Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channel subunits expression. These results suggested that this microRNA could participate in the CAF-induced\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Ca,L<\/jats:sub>\n                      downregulation and in the action potential duration shortening that maintains the arrhythmia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.114.001709","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T23:53:09Z","timestamp":1407541989000},"page":"861-868","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Chronic Atrial Fibrillation Increases MicroRNA-21 in Human Atrial Myocytes Decreasing L-Type Calcium Current"],"prefix":"10.1161","volume":"7","author":[{"given":"Adriana","family":"Barana","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Matamoros","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Dolz-Gait\u00f3n","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"P\u00e9rez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Amor\u00f3s","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sacrist\u00e1n","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Pedraz","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Pinto","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Fern\u00e1ndez-Avil\u00e9s","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Tamargo","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Delp\u00f3n","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Caballero","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), and Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (A.B., M.M., P.D.-G., M.P.-H., I.A., M.N., S.S., J.T., E.D., R.C.), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; and Cardiology and Cardiovascular Surgery Services, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain (\u00c1.P., \u00c1.P., F.F.-A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2009"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46315"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.5.428"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.7.776"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.02.028"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.5.684"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000145659.80212.6a"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2067"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.110.958967"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044906"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0278-0"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0284-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07511"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circep.112.973214"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs313"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2008.03.010"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030933"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-010-9169-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073397"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00111.2011"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.08.014"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.8.5.16154"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2595"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2013.865839"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31822a789b"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00057.2009"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.109.933036"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.11.2968"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.023986"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-007-0174-6"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.08.035"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62185"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055391"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2013.03.014"}],"container-title":["Circulation: Arrhythmia and Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCEP.114.001709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T19:53:55Z","timestamp":1715543635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCEP.114.001709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1161\/CIRCEP.114.001709"],"URL":"https:\/\/doi.org\/10.1161\/circep.114.001709","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718526011.793526296","asserted-by":"object"}]},"ISSN":["1941-3149","1941-3084"],"issn-type":[{"value":"1941-3149","type":"print"},{"value":"1941-3084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10]]},"assertion":[{"value":"2013-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}