Empagliflozin Limits Myocardial Infarction in Vivo and Cell Death in Vitro: Role of STAT3, Mitochondria, and Redox Aspects

• DOI: 10.3389/fphys.2017.01077
• Publication Date: 2017-12-18T23:11:32Z
• Authors: Ioanna Andreadou; Panagiotis Efentakis; Evangelos Balafas; Gabriele Togliatto; Constantinos H. D...; Aimilia Varela; Constantinos A. D...; Panagiota-Efstath...; Eirini Maratou; Vaia Lambadiari; Ignatios Ikonomidis; Nikolaos Kostomit...; Maria F. Brizzi; George Dimitriadis; Efstathios K. Ili...
• Keywords: Empagliflozin

Empagliflozin (EMPA), a drug approved for type 2 diabetes management, reduced cardiovascular death but is unknown if it reduces myocardial infarction. We sought to investigate: (i) the effect of EMPA on function and infarct size after ischemia/reperfusion in mice fed with western diet (WD), (ii) underlying signaling pathways, (iii) its effects cell survival rat embryonic-heart-derived cardiomyoblasts (H9C2) endothelial cells (ECs). To facilitate aforementioned aims, were initially randomized Control groups subjected 30 min ischemia h reperfusion. body weight, blood glucose levels, mean arterial pressure. Cholesterol, triglyceride, AGEs remained unchanged. Left ventricular fractional shortening was improved (43.97 ± 0.92 vs. 40.75 0.61%) (33.2 0.01 17.6 0.02%). In second series experiments, above interventions up 10th reperfusion biopsies obtained assessment cascade. STAT3 increased parallel levels malondialdehyde (MDA) expression iNOS interleukin-6. Cell viability ATP content H9C2 ECs. While, phosphorylation known bestow sparing properties through interaction mitochondria, we observed that did not directly alter mitochondrial calcium retention capacity (CRC); therefore, reducing infarction dependent. conclusion, improves as well redox regulation by decreasing subsequently lipid peroxidation shown surrogate marker MDA. The mechanisms action implicate activation anti-oxidant anti-inflammatory properties.