SGLT2 inhibitors reduce infarct size in reperfused ischemic heart and improve cardiac function during ischemic episodes in preclinical models

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  • Ioanna Andreadou, Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece. Electronic address: jandread@pharm.uoa.gr.
  • ,
  • Robert M Bell, The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
  • ,
  • Hans Erik Bøtker
  • Coert J Zuurbier, Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam Infection & Immunity, Meibergdreef 9, AZ, 1105 Amsterdam, the Netherlands. Electronic address: c.j.zuurbier@amsterdamumc.nl.

The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of effective drugs managing patients, who suffer from type 2 diabetes (T2D): Landmark clinical trials including EMPA-REG, CANVAS and Declare-TIMI have demonstrated that SGLT2 inhibitors reduce cardiovascular mortality and re-hospitalization for heart failure (HF) in patients with T2D. It is well established that there is a strong independent relationship among infarct size measured within 1 month after reperfusion and all-cause death and hospitalization for HF: The fact that cardiovascular mortality was significantly reduced with the SGLT2 inhibitors, fuels the assumption that this class of therapies may attenuate myocardial infarct size. Experimental evidence demonstrates that SGLT2 inhibitors exert cardioprotective effects in animal models of acute myocardial infarction through improved function during the ischemic episode, reduction of infarct size and a subsequent attenuation of heart failure development. The aim of the present review is to outline the current state of preclinical research in terms of myocardial ischemia/reperfusion injury (I/R) and infarct size for clinically available SGLT2 inhibitors and summarize some of the proposed mechanisms of action (lowering intracellular Na+ and Ca2+, NHE inhibition, STAT3 and AMPK activation, CamKII inhibition, reduced inflammation and oxidative stress) that may contribute to the unexpected beneficial cardiovascular effects of this class of compounds.

Original languageEnglish
Article number165770
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue7
Pages (from-to)165770
ISSN0925-4439
DOIs
Publication statusPublished - Jul 2020

Bibliographical note

Copyright © 2020 Elsevier B.V. All rights reserved.

    Research areas

  • Ischemia/reperfusion injury, Molecular signaling, Myocardial infarct size, Sodium-glucose cotransporter 2 inhibitors

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