Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence?
This review summarizes and describes the current evidence addressing how sodium-glucose cotransporter 2 (SGLT2) inhibitors alter the function of sodium-hydrogen exchanger 1 (NHE-1), in association with their protective effects against adverse cardiovascular events. In the heart, SGLT2 inhibitors mod...
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th-mahidol.854422023-06-19T00:41:44Z Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? Wichaiyo S. Mahidol University Medicine This review summarizes and describes the current evidence addressing how sodium-glucose cotransporter 2 (SGLT2) inhibitors alter the function of sodium-hydrogen exchanger 1 (NHE-1), in association with their protective effects against adverse cardiovascular events. In the heart, SGLT2 inhibitors modulate the function of NHE-1 (either by direct inhibition or indirect attenuation of protein expression), which promotes cardiac contraction and an enhanced energy supply, in association with improved mitochondrial function, reduced inflammation/oxidative/endoplasmic reticulum stress, and attenuated fibrosis and apoptotic/autophagic cell death. The vasodilating effect of SGLT2 inhibitors has also been proposed due to NHE-1 inhibition. Moreover, platelet-expressed NHE-1 might serve as a target for SGLT2 inhibitors, since these drugs and selective NHE-1 inhibitors produce comparable activity against adenosine diphosphate-stimulated platelet activation. Overall, it is promising that the modulation of the functions of NHE-1 on the heart, blood vessels, and platelets may act as a contributing pathway for the cardiovascular benefits of SGLT2 inhibitors in diabetes and heart failure. 2023-06-18T17:41:44Z 2023-06-18T17:41:44Z 2022-11-01 Review Heart Failure Reviews Vol.27 No.6 (2022) , 1973-1990 10.1007/s10741-022-10220-2 15737322 13824147 35179683 2-s2.0-85124741231 https://repository.li.mahidol.ac.th/handle/123456789/85442 SCOPUS |
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Medicine Wichaiyo S. Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? |
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This review summarizes and describes the current evidence addressing how sodium-glucose cotransporter 2 (SGLT2) inhibitors alter the function of sodium-hydrogen exchanger 1 (NHE-1), in association with their protective effects against adverse cardiovascular events. In the heart, SGLT2 inhibitors modulate the function of NHE-1 (either by direct inhibition or indirect attenuation of protein expression), which promotes cardiac contraction and an enhanced energy supply, in association with improved mitochondrial function, reduced inflammation/oxidative/endoplasmic reticulum stress, and attenuated fibrosis and apoptotic/autophagic cell death. The vasodilating effect of SGLT2 inhibitors has also been proposed due to NHE-1 inhibition. Moreover, platelet-expressed NHE-1 might serve as a target for SGLT2 inhibitors, since these drugs and selective NHE-1 inhibitors produce comparable activity against adenosine diphosphate-stimulated platelet activation. Overall, it is promising that the modulation of the functions of NHE-1 on the heart, blood vessels, and platelets may act as a contributing pathway for the cardiovascular benefits of SGLT2 inhibitors in diabetes and heart failure. |
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Mahidol University |
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Mahidol University Wichaiyo S. |
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Review |
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Wichaiyo S. |
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Wichaiyo S. |
title |
Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? |
title_short |
Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? |
title_full |
Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? |
title_fullStr |
Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? |
title_full_unstemmed |
Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? |
title_sort |
alterations of sodium-hydrogen exchanger 1 function in response to sglt2 inhibitors: what is the evidence? |
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2023 |
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https://repository.li.mahidol.ac.th/handle/123456789/85442 |
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1781414849523220480 |