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

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1866; no. 7; p. 165770
• Main Authors: Andreadou, Ioanna, Bell, Robert M., Bøtker, Hans Erik, Zuurbier, Coert J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2020
• Subjects: Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - genetics; Cardiovascular Diseases - pathology; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Heart Failure - drug therapy; Heart Failure - etiology; Heart Failure - genetics; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Infarction - drug therapy; Infarction - etiology; Infarction - genetics; Ischemia/reperfusion injury; Molecular signaling; Myocardial infarct size; Risk Factors; Sodium-glucose cotransporter 2 inhibitors; Sodium-Glucose Transporter 2 - genetics; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Molecular signaling; Myocardial infarct size; Ischemia/reperfusion injury; Sodium-glucose cotransporter 2 inhibitors
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2020.165770

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.
•SGLT2 inhibitors exert cardioprotective effects in animal models of acute myocardial infarction•We outline the preclinical research in terms of myocardial I/R for clinically available SGLT2 inhibitors•We outline the proposed mechanisms of action