Empagliflozin reduces arrhythmogenic effects in rat neonatal and human iPSC-derived cardiomyocytes and improves cytosolic calcium handling at least partially independent of NHE1

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSANTOS, Danubia Silva dos
dc.contributor.authorTURACA, Lauro Thiago
dc.contributor.authorCOUTINHO, Keyla Cristiny da Silva
dc.contributor.authorBARBOSA, Raiana Andrade Quintanilha
dc.contributor.authorPOLIDORO, Juliano Zequini
dc.contributor.authorKASAI-BRUNSWICK, Tais Hanae
dc.contributor.authorCARVALHO, Antonio Carlos Campos de
dc.contributor.authorGIRARDI, Adriana Castello Costa
dc.date.accessioned2023-08-16T18:04:07Z
dc.date.available2023-08-16T18:04:07Z
dc.date.issued2023
dc.description.abstractThe antidiabetic agent class of sodium-glucose cotransporter 2 (SGLT2) inhibitors confer unprecedented cardiovascular benefits beyond glycemic control, including reducing the risk of fatal ventricular arrhythmias. However, the impact of SGLT2 inhibitors on the electrophysiological properties of cardiomyocytes exposed to stimuli other than hyperglycemia remains elusive. This investigation tested the hypothesis that the SGLT2 inhibitor empagliflozin (EMPA) affects cardiomyocyte electrical activity under hypoxic conditions. Rat neonatal and human induced pluripotent stem cell (iPSC)-derived cardiomyocytes incubated or not with the hypoxia-mimetic agent CoCl2 were treated with EMPA (1 mu M) or vehicle for 24 h. Action potential records obtained using intracellular microelectrodes demonstrated that EMPA reduced the action potential duration at 30%, 50%, and 90% repolarization and arrhythmogenic events in rat and human cardiomyocytes under normoxia and hypoxia. Analysis of Ca2+ transients using Fura-2-AM and contractility kinetics showed that EMPA increased Ca2+ transient amplitude and decreased the half-time to recover Ca2+ transients and relaxation time in rat neonatal cardiomyocytes. We also observed that the combination of EMPA with the Na+/H+ exchanger isoform 1 (NHE1) inhibitor cariporide (10 mu M) exerted a more pronounced effect on Ca2+ transients and contractility than either EMPA or cariporide alone. Besides, EMPA, but not cariporide, increased phospholamban phosphorylation at serine 16. Collectively, our data reveal that EMPA reduces arrhythmogenic events, decreases the action potential duration in rat neonatal and human cardiomyocytes under normoxic or hypoxic conditions, and improves cytosolic calcium handling at least partially independent of NHE1. Moreover, we provided further evidence that SGLT2 inhibitor-mediated cardioprotection may be partly attributed to its cardiomyocyte electrophysiological effects.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.identifier.citationSCIENTIFIC REPORTS, v.13, n.1, 2023
dc.identifier.doi10.1038/s41598-023-35944-5
dc.identifier.issn2045-2322
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/54875
dc.language.isoeng
dc.publisherNATURE PORTFOLIOeng
dc.relation.ispartofScientific Reports
dc.rightsopenAccesseng
dc.rights.holderCopyright NATURE PORTFOLIOeng
dc.subject.otherglucose cotransporter 2eng
dc.subject.othercardiac na+/h+ exchangereng
dc.subject.otherheart-failureeng
dc.subject.otherventricular-arrhythmiaseng
dc.subject.otherdiastolic dysfunctioneng
dc.subject.othersglt2 inhibitorseng
dc.subject.othersodiumeng
dc.subject.othermodeleng
dc.subject.otherphosphorylationeng
dc.subject.otherphospholambaneng
dc.subject.wosMultidisciplinary Scienceseng
dc.titleEmpagliflozin reduces arrhythmogenic effects in rat neonatal and human iPSC-derived cardiomyocytes and improves cytosolic calcium handling at least partially independent of NHE1eng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalCOUTINHO, Keyla Cristiny da Silva:Univ Fed Rio De Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, Brazil
hcfmusp.author.externalBARBOSA, Raiana Andrade Quintanilha:Univ Fed Rio De Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, Brazil; Inst Nacl Cardiol, Ctr Tecnol Celular, Rio De Janeiro, Brazil
hcfmusp.author.externalKASAI-BRUNSWICK, Tais Hanae:Univ Fed Rio De Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, Brazil; Univ Fed Rio De Janeiro, Ctr Nacl Biol Estrutural & Bioimagem CENABIO, Rio De Janeiro, RJ, Brazil
hcfmusp.author.externalCARVALHO, Antonio Carlos Campos de:Univ Fed Rio De Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, Brazil; Univ Fed Rio De Janeiro, Ctr Nacl Biol Estrutural & Bioimagem CENABIO, Rio De Janeiro, RJ, Brazil
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcDANUBIA SILVA DOS SANTOS
hcfmusp.contributor.author-fmusphcLAURO THIAGO TURACA
hcfmusp.contributor.author-fmusphcJULIANO ZEQUINI POLIDORO
hcfmusp.contributor.author-fmusphcADRIANA CASTELLO COSTA GIRARDI
hcfmusp.description.issue1
hcfmusp.description.volume13
hcfmusp.origemWOS
hcfmusp.origem.pubmed37248416
hcfmusp.origem.scopus2-s2.0-85160466790
hcfmusp.origem.wosWOS:000999237500025
hcfmusp.publisher.cityBERLINeng
hcfmusp.publisher.countryGERMANYeng
hcfmusp.relation.referenceAimond F, 1999, CARDIOVASC RES, V42, P402, DOI 10.1016/S0008-6363(99)00070-Xeng
hcfmusp.relation.referenceAnker SD, 2021, NEW ENGL J MED, V385, P1451, DOI 10.1056/NEJMoa2107038eng
hcfmusp.relation.referenceAntoniou CK, 2017, EUR CARDIOL REV, V12, P112, DOI 10.15420/ecr.2017:16:1eng
hcfmusp.relation.referenceAntzelevitch Charles, 2011, Card Electrophysiol Clin, V3, P23, DOI 10.1016/j.ccep.2010.10.012eng
hcfmusp.relation.referenceAzam MA, 2021, LIFE SCI, V276, DOI 10.1016/j.lfs.2021.119440eng
hcfmusp.relation.referenceBaartscheer A, 2003, CARDIOVASC RES, V58, P99, DOI 10.1016/S0008-6363(02)00854-4eng
hcfmusp.relation.referenceBaartscheer A, 2017, DIABETOLOGIA, V60, P568, DOI 10.1007/s00125-016-4134-xeng
hcfmusp.relation.referenceBartos DC, 2015, COMPR PHYSIOL, V5, P1423, DOI 10.1002/cphy.c140069eng
hcfmusp.relation.referenceBelardinelli L, 2006, HEART, V92, P6, DOI 10.1136/hrt.2005.078790eng
hcfmusp.relation.referenceBers DM, 2014, ANNU REV PHYSIOL, V76, P107, DOI 10.1146/annurev-physiol-020911-153308eng
hcfmusp.relation.referenceBorges AA, 2021, J AM SOC NEPHROL, V32, P1616, DOI 10.1681/ASN.2020071029eng
hcfmusp.relation.referenceChiriaco M, 2022, CURR OPIN PHARMACOL, V66, DOI 10.1016/j.coph.2022.102272eng
hcfmusp.relation.referenceChung YJ, 2021, CARDIOVASC RES, V117, P2794, DOI 10.1093/cvr/cvaa323eng
hcfmusp.relation.referenceColyer J, 1998, ANN NY ACAD SCI, V853, P79, DOI 10.1111/j.1749-6632.1998.tb08258.xeng
hcfmusp.relation.referenceCordeiro JM, 2013, J MOL CELL CARDIOL, V60, P36, DOI 10.1016/j.yjmcc.2013.03.014eng
hcfmusp.relation.referenceCurtain JP, 2021, EUR HEART J, V42, P3727, DOI 10.1093/eurheartj/ehab560eng
hcfmusp.relation.referenceDavia K, 2001, J MOL CELL CARDIOL, V33, P1005, DOI 10.1006/jmcc.2001.1368eng
hcfmusp.relation.referenceDespa S, 2012, CARDIOVASC RES, V95, P480, DOI 10.1093/cvr/cvs213eng
hcfmusp.relation.referencedos Santos DS, 2020, AM J PHYSIOL-CELL PH, V318, pC328, DOI 10.1152/ajpcell.00275.2019eng
hcfmusp.relation.referenceDyck JRB, 2022, J MOL CELL CARDIOL, V167, P17, DOI 10.1016/j.yjmcc.2022.03.005eng
hcfmusp.relation.referenceEroglu TE, 2022, EUR HEART J-CARD PHA, V9, P18, DOI 10.1093/ehjcvp/pvac043eng
hcfmusp.relation.referenceFrank K, 2000, ANN MED, V32, P572, DOI 10.3109/07853890008998837eng
hcfmusp.relation.referenceGhezzi C, 2017, J AM SOC NEPHROL, V28, P802, DOI 10.1681/ASN.2016050510eng
hcfmusp.relation.referenceGrandy SA, 2007, AM J PHYSIOL-HEART C, V293, pH2168, DOI 10.1152/ajpheart.00521.2007eng
hcfmusp.relation.referenceHammoudi N, 2017, CARDIOVASC DRUG THER, V31, P233, DOI 10.1007/s10557-017-6734-1eng
hcfmusp.relation.referenceHegyi B, 2022, CIRCULATION, V145, P1029, DOI 10.1161/CIRCULATIONAHA.121.057237eng
hcfmusp.relation.referenceJanse MJ, 2001, J CARDIOVASC ELECTR, V12, P496, DOI 10.1046/j.1540-8167.2001.00496.xeng
hcfmusp.relation.referenceJeevaratnam K, 2018, J CARDIOVASC PHARM T, V23, P119, DOI 10.1177/1074248417729880eng
hcfmusp.relation.referenceJensen L, 2018, J CELL PHYSIOL, V233, P5420, DOI 10.1002/jcp.26380eng
hcfmusp.relation.referenceJoukar S, 2021, LAB ANIM RES, V37, DOI 10.1186/s42826-021-00102-3eng
hcfmusp.relation.referenceKaab S, 1998, CIRCULATION, V98, P1383, DOI 10.1161/01.CIR.98.14.1383eng
hcfmusp.relation.referenceKarmazyn M, 1999, CIRC RES, V85, P777, DOI 10.1161/01.RES.85.9.777eng
hcfmusp.relation.referenceKarpushev AV, 2022, INT J MOL SCI, V23, DOI 10.3390/ijms23179559eng
hcfmusp.relation.referenceKolesnik E, 2022, INT J MOL SCI, V23, DOI 10.3390/ijms23031678eng
hcfmusp.relation.referenceKolijn D, 2021, CARDIOVASC RES, V117, P495, DOI 10.1093/cvr/cvaa123eng
hcfmusp.relation.referenceKorhonen T, 2009, BIOPHYS J, V96, P1189, DOI 10.1016/j.bpj.2008.10.026eng
hcfmusp.relation.referenceLee JH, 2017, CELL STEM CELL, V21, P179, DOI 10.1016/j.stem.2017.07.003eng
hcfmusp.relation.referenceLee TI, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20071680eng
hcfmusp.relation.referenceLi HL, 2021, CARDIOVASC DIABETOL, V20, DOI 10.1186/s12933-021-01293-8eng
hcfmusp.relation.referenceLi X, 2021, J AM HEART ASSOC, V10, DOI 10.1161/JAHA.120.018298eng
hcfmusp.relation.referenceLian XJ, 2013, NAT PROTOC, V8, P162, DOI 10.1038/nprot.2012.150eng
hcfmusp.relation.referenceLuo M, 2013, CIRC RES, V113, P690, DOI 10.1161/CIRCRESAHA.113.301651eng
hcfmusp.relation.referenceMaier LS, 2009, J CARDIOVASC PHARM, V54, P279, DOI 10.1097/FJC.0b013e3181a1b9e7eng
hcfmusp.relation.referenceMattiazzi A, 2005, CARDIOVASC RES, V68, P366, DOI 10.1016/j.cardiores.2005.08.010eng
hcfmusp.relation.referenceMcMurray JJV, 2019, NEW ENGL J MED, V381, P1995, DOI 10.1056/NEJMoa1911303eng
hcfmusp.relation.referenceMesquita FCP, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-55837-weng
hcfmusp.relation.referenceMustroph J, 2018, ESC HEART FAIL, V5, P642, DOI 10.1002/ehf2.12336eng
hcfmusp.relation.referenceNeal B, 2017, NEW ENGL J MED, V377, P644, DOI 10.1056/NEJMoa1611925eng
hcfmusp.relation.referencePabel S, 2018, EUR J HEART FAIL, V20, P1690, DOI 10.1002/ejhf.1328eng
hcfmusp.relation.referencePacker M, 2020, CIRC-HEART FAIL, V13, DOI 10.1161/CIRCHEARTFAILURE.120.007197eng
hcfmusp.relation.referencePacker M, 2020, NEW ENGL J MED, V383, P1413, DOI 10.1056/NEJMoa2022190eng
hcfmusp.relation.referencePacker M, 2017, JAMA CARDIOL, V2, P1025, DOI 10.1001/jamacardio.2017.2275eng
hcfmusp.relation.referencePhilippaert K, 2021, CIRCULATION, V143, P2188, DOI 10.1161/CIRCULATIONAHA.121.053350eng
hcfmusp.relation.referencePogwizd SM, 2003, CARDIOVASC RES, V57, P887, DOI 10.1016/S0008-6363(02)00735-6eng
hcfmusp.relation.referenceQuentin V, 2022, WORLD J DIABETES, V13, P683, DOI 10.4239/wjd.v13.i9.683eng
hcfmusp.relation.referenceRao V, 2014, BIOPHYS J, V107, P1196, DOI 10.1016/j.bpj.2014.07.027eng
hcfmusp.relation.referenceRavens U, 2008, EUROPACE, V10, P1133, DOI 10.1093/europace/eun193eng
hcfmusp.relation.referenceScalzo S, 2021, CELL REP METHODS, V1, DOI 10.1016/j.crmeth.2021.100044eng
hcfmusp.relation.referenceScalzo Sergio, 2022, STAR Protoc, V3, P101144, DOI 10.1016/j.xpro.2022.101144eng
hcfmusp.relation.referenceScheen AJ, 2014, CLIN PHARMACOKINET, V53, P213, DOI 10.1007/s40262-013-0126-xeng
hcfmusp.relation.referenceTrum M, 2020, ESC HEART FAIL, V7, P4429, DOI 10.1002/ehf2.13024eng
hcfmusp.relation.referenceUthman L, 2019, CARDIOVASC RES, V115, P1533, DOI 10.1093/cvr/cvz004eng
hcfmusp.relation.referenceUthman L, 2018, DIABETOLOGIA, V61, P722, DOI 10.1007/s00125-017-4509-7eng
hcfmusp.relation.referenceVallon V, 2011, J AM SOC NEPHROL, V22, P104, DOI 10.1681/ASN.2010030246eng
hcfmusp.relation.referenceVenturini G, 2023, FRONT CELL INFECT MI, V13, DOI 10.3389/fcimb.2023.1098457eng
hcfmusp.relation.referenceVerma S, 2016, DIABETES CARE, V39, pE212, DOI 10.2337/dc16-1312eng
hcfmusp.relation.referenceWagner S, 2015, CIRC RES, V116, P1956, DOI 10.1161/CIRCRESAHA.116.304678eng
hcfmusp.relation.referenceWiviott SD, 2019, NEW ENGL J MED, V380, P347, DOI 10.1056/NEJMoa1812389eng
hcfmusp.relation.referenceXue GL, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.988408eng
hcfmusp.relation.referenceYokoyama H, 2000, J AM COLL CARDIOL, V36, P534, DOI 10.1016/S0735-1097(00)00730-0eng
hcfmusp.relation.referenceZinman B, 2016, NEW ENGL J MED, V374, P1094, DOI 10.1056/NEJMc1600827eng
hcfmusp.relation.referenceZuurbier CJ, 2021, CARDIOVASC RES, V117, P2699, DOI 10.1093/cvr/cvab129eng
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