Role and molecular mechanisms of SGLT2 inhibitors in pathological cardiac remodeling (Review)

Abstract

Cardiovascular diseases are caused by pathological cardiac remodeling, which involves fibrosis, inflammation and cell dysfunction. This includes autophagy, apoptosis, oxidative stress, mitochondrial dysfunction, changes in energy metabolism, angiogenesis and dysregulation of signaling pathways. These changes in heart structure and/or function ultimately result in heart failure. In an effort to prevent this, multiple cardiovascular outcome trials have demonstrated the cardiac benefits of sodium-glucose cotransporter type 2 inhibitors (SGLT2is), hypoglycemic drugs initially designed to treat type 2 diabetes mellitus. SGLT2is include empagliflozin and dapagliflozin, which are listed as guideline drugs in the 2021 European Guidelines for Heart Failure and the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America Guidelines for Heart Failure Management. In recent years, multiple studies using animal models have explored the mechanisms by which SGLT2is prevent cardiac remodeling. This article reviews the role of SGLT2is in cardiac remodeling induced by different etiologies to provide a guideline for further evaluation of the mechanisms underlying the inhibition of pathological cardiac remodeling by SGLT2is, as well as the development of novel drug targets.