Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression

<p>Diabetes mellitus (DM)-induced cardiac morbidities have been the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors including empagliflozin (EMPA), which have been approved for the treatment of DM, have gained attention for their car...

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Main Author: Nabeel Abdulrahman (725914) (author)
Other Authors: Meram Ibrahim (14151348) (author), Jensa Mariam Joseph (14151351) (author), Hanan Mahmoud Elkoubatry (14151354) (author), Al-Anood Al-Shamasi (14151357) (author), Menatallah Rayan (14151360) (author), Alain Pierre Gadeau (14151363) (author), Rashid Ahmed (3900679) (author), Hussein Eldassouki (14151366) (author), Anwarul Hasan (1332066) (author), Fatima Mraiche (715733) (author)
Published: 2022
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_version_ 1864513567574720512
author Nabeel Abdulrahman (725914)
author2 Meram Ibrahim (14151348)
Jensa Mariam Joseph (14151351)
Hanan Mahmoud Elkoubatry (14151354)
Al-Anood Al-Shamasi (14151357)
Menatallah Rayan (14151360)
Alain Pierre Gadeau (14151363)
Rashid Ahmed (3900679)
Hussein Eldassouki (14151366)
Anwarul Hasan (1332066)
Fatima Mraiche (715733)
author2_role author
author
author
author
author
author
author
author
author
author
author_facet Nabeel Abdulrahman (725914)
Meram Ibrahim (14151348)
Jensa Mariam Joseph (14151351)
Hanan Mahmoud Elkoubatry (14151354)
Al-Anood Al-Shamasi (14151357)
Menatallah Rayan (14151360)
Alain Pierre Gadeau (14151363)
Rashid Ahmed (3900679)
Hussein Eldassouki (14151366)
Anwarul Hasan (1332066)
Fatima Mraiche (715733)
author_role author
dc.creator.none.fl_str_mv Nabeel Abdulrahman (725914)
Meram Ibrahim (14151348)
Jensa Mariam Joseph (14151351)
Hanan Mahmoud Elkoubatry (14151354)
Al-Anood Al-Shamasi (14151357)
Menatallah Rayan (14151360)
Alain Pierre Gadeau (14151363)
Rashid Ahmed (3900679)
Hussein Eldassouki (14151366)
Anwarul Hasan (1332066)
Fatima Mraiche (715733)
dc.date.none.fl_str_mv 2022-11-22T21:13:52Z
dc.identifier.none.fl_str_mv 10.1007/s11010-022-04411-6
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Empagliflozin_inhibits_angiotensin_II-induced_hypertrophy_in_H9c2_cardiomyoblasts_through_inhibition_of_NHE1_expression/21597393
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biochemistry and cell biology
Medical biochemistry and metabolomics
Cell Biology
Clinical Biochemistry
Molecular Biology
General Medicine
dc.title.none.fl_str_mv Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p>Diabetes mellitus (DM)-induced cardiac morbidities have been the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors including empagliflozin (EMPA), which have been approved for the treatment of DM, have gained attention for their cardioprotective effect. The mechanism by which SGLT-2 inhibitors exert their cardioprotective effect remains unclear. Recent studies have suggested that EMPA exerts its cardioprotective effect by inhibiting the Na+/H+ exchanger (NHE), a group of membrane proteins that regulate intracellular pH and cell volume. Increased activity and expression of NHE isoform 1 (NHE1), the predominant isoform expressed in the heart, leads to cardiac hypertrophy. p90 ribosomal s6 kinase (p90 RSK) has been demonstrated to stimulate NHE1 activity. In our study, H9c2 cardiomyoblasts were treated with angiotensin II (ANG) to activate NHE1 and generate a hypertrophic model. We aimed to understand whether EMPA reverses the ANG-induced hypertrophic response and to elucidate the molecular pathway contributing to the cardioprotective effect of EMPA. Our study demonstrated that ANG-induced hypertrophy of H9c2 cardiomyoblasts is accompanied with increased SGLT-1 and NHE1 protein expression, an effect which is prevented in the presence of EMPA. EMPA reduces ANG-induced hypertrophy through the inhibition of SGLT-1 and NHE1 expression.</p><h2>Other Information</h2> <p> Published in: Molecular and Cellular Biochemistry<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1007/s11010-022-04411-6" target="_blank">http://dx.doi.org/10.1007/s11010-022-04411-6</a></p>
eu_rights_str_mv openAccess
id Manara2_f040c19b183cfd62983a34630346571a
identifier_str_mv 10.1007/s11010-022-04411-6
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/21597393
publishDate 2022
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rights_invalid_str_mv CC BY 4.0
spelling Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expressionNabeel Abdulrahman (725914)Meram Ibrahim (14151348)Jensa Mariam Joseph (14151351)Hanan Mahmoud Elkoubatry (14151354)Al-Anood Al-Shamasi (14151357)Menatallah Rayan (14151360)Alain Pierre Gadeau (14151363)Rashid Ahmed (3900679)Hussein Eldassouki (14151366)Anwarul Hasan (1332066)Fatima Mraiche (715733)Biochemistry and cell biologyMedical biochemistry and metabolomicsCell BiologyClinical BiochemistryMolecular BiologyGeneral Medicine<p>Diabetes mellitus (DM)-induced cardiac morbidities have been the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors including empagliflozin (EMPA), which have been approved for the treatment of DM, have gained attention for their cardioprotective effect. The mechanism by which SGLT-2 inhibitors exert their cardioprotective effect remains unclear. Recent studies have suggested that EMPA exerts its cardioprotective effect by inhibiting the Na+/H+ exchanger (NHE), a group of membrane proteins that regulate intracellular pH and cell volume. Increased activity and expression of NHE isoform 1 (NHE1), the predominant isoform expressed in the heart, leads to cardiac hypertrophy. p90 ribosomal s6 kinase (p90 RSK) has been demonstrated to stimulate NHE1 activity. In our study, H9c2 cardiomyoblasts were treated with angiotensin II (ANG) to activate NHE1 and generate a hypertrophic model. We aimed to understand whether EMPA reverses the ANG-induced hypertrophic response and to elucidate the molecular pathway contributing to the cardioprotective effect of EMPA. Our study demonstrated that ANG-induced hypertrophy of H9c2 cardiomyoblasts is accompanied with increased SGLT-1 and NHE1 protein expression, an effect which is prevented in the presence of EMPA. EMPA reduces ANG-induced hypertrophy through the inhibition of SGLT-1 and NHE1 expression.</p><h2>Other Information</h2> <p> Published in: Molecular and Cellular Biochemistry<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1007/s11010-022-04411-6" target="_blank">http://dx.doi.org/10.1007/s11010-022-04411-6</a></p>2022-11-22T21:13:52ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11010-022-04411-6https://figshare.com/articles/journal_contribution/Empagliflozin_inhibits_angiotensin_II-induced_hypertrophy_in_H9c2_cardiomyoblasts_through_inhibition_of_NHE1_expression/21597393CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215973932022-11-22T21:13:52Z
spellingShingle Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
Nabeel Abdulrahman (725914)
Biochemistry and cell biology
Medical biochemistry and metabolomics
Cell Biology
Clinical Biochemistry
Molecular Biology
General Medicine
status_str publishedVersion
title Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
title_full Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
title_fullStr Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
title_full_unstemmed Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
title_short Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
title_sort Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression
topic Biochemistry and cell biology
Medical biochemistry and metabolomics
Cell Biology
Clinical Biochemistry
Molecular Biology
General Medicine