Empagliflozin restored the beneficial effect of cardiac microvascular endothelial cells on cardiomyocyte contraction and relaxation by reducing TNF-α-induced reactive oxygen species accumulation.
Does empagliflozin restore cardiomyocyte function impaired by inflammation-induced cardiac microvascular endothelial cell dysfunction?
Empagliflozin restores cardiomyocyte function impaired by inflammation-induced microvascular endothelial dysfunction, providing a potential mechanism for its clinical benefits in HFpEF.
The positive findings of the EMPA-REG OUTCOME trial (Randomized, Placebo-Controlled Cardiovascular Outcome Trial of Empagliflozin) on heart failure (HF) outcome in patients with type 2 diabetes mellitus suggest a direct effect of empagliflozin on the heart. These patients frequently have HF with preserved ejection fraction (HFpEF), in which a metabolic risk-related pro-inflammatory state induces cardiac microvascular endothelial cell (CMEC) dysfunction with subsequent cardiomyocyte (CM) contractility impairment. This study showed that CMECs confer a direct positive effect on contraction and relaxation of CMs, an effect that requires nitric oxide, is diminished after CMEC stimulation with tumor necrosis factor-α, and is restored by empagliflozin. Our findings on the effect of empagliflozin on CMEC-mediated preservation of CM function suggests that empagliflozin can be used to treat the cardiac mechanical implications of microvascular dysfunction in HFpEF.
Juni et al. (Sun,) conducted a other in Heart failure with preserved ejection fraction (preclinical model). Empagliflozin vs. TNF-α alone was evaluated on Cardiomyocyte contraction and relaxation. Empagliflozin restored the beneficial effect of cardiac microvascular endothelial cells on cardiomyocyte contraction and relaxation by reducing TNF-α-induced reactive oxygen species accumulation.