Empagliflozin attenuated adverse cardiac remodeling and improved mitochondria-related cellular energetics independently of Parkin in mice subjected to permanent coronary artery ligation.
Does empagliflozin attenuate adverse postinfarction left ventricular remodeling in wild-type and Parkin knockout mice?
Empagliflozin attenuates adverse postinfarction left ventricular remodeling and improves mitochondrial energetics independently of Parkin, suggesting a potential therapeutic pathway for patients with mitophagy-related deficiencies.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors such as empagliflozin are known to reduce the risk of hospitalizations related to heart failure irrespective of diabetic state. Meanwhile, adverse cardiac remodeling remains the leading cause of heart failure and death in the USA. Thus, understanding the mechanisms that are responsible for the beneficial effects of SGLT2 inhibitors is of the utmost relevance and importance. Our previous work illustrated a connection between adverse cardiac remodeling and the regulation of mitochondrial turnover and cellular energetics using a short-acting glucagon-like peptide-1 receptor agonist (GLP1Ra). Here, we sought to determine if the mechanism of the SGLT2 inhibitor empagliflozin (EMPA) in ameliorating adverse remodeling was similar and/or to identify what differences exist, if any. To this end, we administered permanent coronary artery ligation to induce adverse remodeling in wild-type and Parkin knockout mice and examined the progression of adverse cardiac remodeling with or without EMPA treatment over time. Like GLP1Ra, we found that EMPA affords a robust attenuation of PCAL-induced adverse remodeling. Interestingly, unlike the GLP1Ra, EMPA does not require Parkin to improve/maintain mitochondria-related cellular energetics and afford its benefits against developing adverse remodeling. These findings suggests that further investigation of EMPA is warranted as a potential path for developing therapy against adverse cardiac remodeling for patients that may have Parkin and/or mitophagy-related deficiencies.
Song et al. (Fri,) conducted a other in Adverse postinfarction left ventricular remodeling. Empagliflozin (EMPA) vs. No EMPA treatment was evaluated on Progression of adverse cardiac remodeling. Empagliflozin attenuated adverse cardiac remodeling and improved mitochondria-related cellular energetics independently of Parkin in mice subjected to permanent coronary artery ligation.