DIRECT EFFECTS OF EMPAGUFLOZIN ON EXTRACELLULAR MATRIX REMODELING IN HUMAN CARDIAC FIBROBLASTS: NOVEL TRANSLATIONAL CLUES TO EMPA-REG OUTCOME

摘要

BACKGROUND: Empagliflozin is an SGLT2 inhibitor that reduced cardiovascular mortality by 38% (EMPA-REG OUTCOME study) in association with a reduction in heart failure related events. The mechanism(s) underlying the heart failure protective effects of empagliflozin remain elusive. Defining this mechanism may have important translational implications for the development of novel medical therapies to treat heart failure. Cardiac fibroblasts play an essential role in progression of structural remodeling and heart failure, in part, by regulating extracellular matrix (ECM) homeostasis. In the present study, we hypothesized that the therapeutic benefits of empagliflozin may be explained by a direct effect on human cardiac fibroblast-mediated collagen remodeling.