Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence?
Issued Date
2022-11-01
Resource Type
ISSN
13824147
eISSN
15737322
Scopus ID
2-s2.0-85124741231
Pubmed ID
35179683
Journal Title
Heart Failure Reviews
Volume
27
Issue
6
Start Page
1973
End Page
1990
Rights Holder(s)
SCOPUS
Bibliographic Citation
Heart Failure Reviews Vol.27 No.6 (2022) , 1973-1990
Suggested Citation
Wichaiyo S., Saengklub N. Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence?. Heart Failure Reviews Vol.27 No.6 (2022) , 1973-1990. 1990. doi:10.1007/s10741-022-10220-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85442
Title
Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence?
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
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.