Grant: Travel Awards - Institute Community Support

BACKGROUND: Cardiovascular disease is a major complication of diabetes and the leading cause of death in diabetic patients. A recent clinical trial study revealed that a diabetes drug called empagliflozin demonstrated unprecedented cardioprotective effects, particularly on cardiovascular death and heart-failure (EMPA-REG OUTCOME study). However, the mechanisms underlying these heart failure protective effects of empagliflozin remain largely unknown. Heart failure is characterized by changes in the biology of a tissue microenvironment called the extracellular matrix (ECM), which is responsible for the overall tissue structure and function. Cardiac fibroblasts are critical mediators of the ECM and play an integral role in the progression of structural cardiac remodeling and heart failure. RESEARCH SUMMARY & SIGNIFICANCE: In this study, using models that mimic the heart ECM, we provide novel data showing a direct effect of empagliflozin on human cardiac fibroblasts resulting in attenuation of their activity and cell-mediated ECM remodeling. We provide critical insights into the profound effects of empagliflozin as noted in the EMPA-REG OUTCOME study which may have important translational implications for the development of novel medical therapies to treat heart failure.