The Role of Empagliflozin in Cardiac Fibroblast-Mediated Extracellular Matrix Remodeling
Abstract
Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has shown remarkable reductions in cardiovascular mortality and heart failure admissions (EMPA-REG OUTCOME). However, the mechanism underlying the heart failure protective effects of empagliflozin remains largely unknown. Cardiac fibroblasts play an integral role in the progression of structural cardiac remodelling and heart failure, in part, by regulating extracellular matrix (ECM) homeostasis. Thus, in this study we sought to determine if empagliflozin has a direct effect on human cardiac fibroblast-mediated ECM remodelling. Empagliflozin attenuated myofibroblast activation as determined by collagen gel contraction and α-smooth muscle actin (α-SMA) characterization. Examination with confocal microscopy revealed cell morphology indicative of a quiescent phenotype and an attenuation of local ECM remodelling by these fibroblasts in response to empagliflozin. Furthermore, gene expression profiling indicated suppression of critical pro-fibrotic markers by empagliflozin. Taken together, we provide critical insights into the profound clinical benefits of empagliflozin on cardiac failure and mortality.
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