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Article: Empagliflozin Ammeliorates High Glucose Induced-Cardiac Dysfuntion in Human iPSC-Derived Cardiomyocytes

TitleEmpagliflozin Ammeliorates High Glucose Induced-Cardiac Dysfuntion in Human iPSC-Derived Cardiomyocytes
Authors
Issue Date2018
PublisherNature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2018, v. 8 n. 1, article no.14872 How to Cite?
AbstractEmpagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart failure and sudden cardiac death but the underlying mechanisms remain elusive. In cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus, heart failure, and myocardial infarction. We hypothesise that empagliflozin exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy. To test this hypothesis, cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were used to test the potential effects of empagliflozin on neutralization of cardiac dysfunction induced by diabetic-like cultures. Our results indicated that insulin-free high glucose culture significantly increased the size of and NPPB, SGLT1 and SGLT2 expression of hiPSC-derived cardiomyocytes. In addition, high glucose-treated hiPSC-derived cardiomyocytes exhibited reduced contractility regardless of the increased calcium transient capacity. Interestingly, application of empagliflozin before or after high glucose treatment effectively reduced the high glucose-induced cardiac abnormalities. Since application of empagliflozin did not significantly alter viability or glycolytic capacity of the hiPSC-derived cardiomyocytes, it is plausible that empagliflozin exerts its effects via the down-regulation of SGLT1, SGLT2 and GLUT1 expression. These observations provide supportive evidence that may help explain its unexpected benefit observed in the EMPA-REG trial.
Persistent Identifierhttp://hdl.handle.net/10722/264234
ISSN
2019 Impact Factor: 3.998
2015 SCImago Journal Rankings: 2.073
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, KM-
dc.contributor.authorLau, VYM-
dc.contributor.authorVidhu, D-
dc.contributor.authorCai, Z-
dc.contributor.authorLee, YK-
dc.contributor.authorLai, KWH-
dc.contributor.authorTse, HF-
dc.contributor.authorSiu, DCW-
dc.date.accessioned2018-10-22T07:51:41Z-
dc.date.available2018-10-22T07:51:41Z-
dc.date.issued2018-
dc.identifier.citationScientific Reports, 2018, v. 8 n. 1, article no.14872-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/264234-
dc.description.abstractEmpagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart failure and sudden cardiac death but the underlying mechanisms remain elusive. In cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus, heart failure, and myocardial infarction. We hypothesise that empagliflozin exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy. To test this hypothesis, cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were used to test the potential effects of empagliflozin on neutralization of cardiac dysfunction induced by diabetic-like cultures. Our results indicated that insulin-free high glucose culture significantly increased the size of and NPPB, SGLT1 and SGLT2 expression of hiPSC-derived cardiomyocytes. In addition, high glucose-treated hiPSC-derived cardiomyocytes exhibited reduced contractility regardless of the increased calcium transient capacity. Interestingly, application of empagliflozin before or after high glucose treatment effectively reduced the high glucose-induced cardiac abnormalities. Since application of empagliflozin did not significantly alter viability or glycolytic capacity of the hiPSC-derived cardiomyocytes, it is plausible that empagliflozin exerts its effects via the down-regulation of SGLT1, SGLT2 and GLUT1 expression. These observations provide supportive evidence that may help explain its unexpected benefit observed in the EMPA-REG trial.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleEmpagliflozin Ammeliorates High Glucose Induced-Cardiac Dysfuntion in Human iPSC-Derived Cardiomyocytes-
dc.typeArticle-
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hk-
dc.identifier.emailLau, VYM: vymlau@hku.hk-
dc.identifier.emailLee, YK: carol801@hku.hk-
dc.identifier.emailLai, KWH: kwhlai@hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailSiu, DCW: cwdsiu@hkucc.hku.hk-
dc.identifier.authorityNg, KM=rp01670-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authoritySiu, DCW=rp00534-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41598-018-33293-2-
dc.identifier.pmid30291295-
dc.identifier.pmcidPMC6173708-
dc.identifier.scopuseid_2-s2.0-85054422227-
dc.identifier.hkuros295697-
dc.identifier.volume8-
dc.identifier.issue1-
dc.identifier.spagearticle no.14872-
dc.identifier.epagearticle no.14872-
dc.identifier.isiWOS:000446501400022-
dc.publisher.placeUnited Kingdom-

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