Empagliflozin in Acute Myocardial Infarction Reduces No-Reflow and Preserves Cardiac Function by Preventing Endothelial Damage
Panagiota Nikolaou, Lara S. F. Konijnenberg, Ioannis V. Kostopoulos, Marios Miliotis, Nikolaos Mylonas, Anastasios D. Georgoulis, George Pavlidis, Carolien Kuster, Vince P.A. van Reijmersdal, Tom T J Luiken, Anna Agapaki, Rona Roverts, N Orologas, Dimitris Grigoriadis, G Pallot, Pierre Boucher, Nikolaos Kostomitsopoulos, Michael Pieper, Stéphane Germain, Yannis L. Loukas, Yannis Dotsikas, Ignatios Ikonomidis, Artemis G. Hatzigeorgiou, Ourania Tsitsilonis, Coert J. Zuurbier, Robin Nijveldt, Niels van Royen, Ioanna Andreadou
Abstract
• Empagliflozin pretreatment reverses the deregulated transcriptome of endothelial cells 2 hours after reperfusion in a mouse model of acute myocardial infarction. • Empagliflozin treatment after acute myocardial infarction has cardioprotective potential similar to pretreatment, which is indicated by the reduced no-reflow phenomenon and infarct size and the preservation of myocardial function. • Besides the preservation of endothelium integrity, empagliflozin treatment leads to reduced neutrophil and inflammatory monocyte infiltration in the heart and attenuates matrix metalloproteinase-2 and intercellular adhesion molecule-1 protein levels 48 hours after reperfusion. • Diabetic patients receiving empagliflozin after acute myocardial infarction presented with improved endothelial glycocalyx thickness and percentage global longitudinal strain, increased flow-mediated dilation, preserved pulse wave velocity, and reduced intercellular adhesion molecule 1 circulating levels at 4- and 12-month follow-ups. Empagliflozin treatment before acute myocardial infarction mainly targets the endothelial cell transcriptome. Empagliflozin treatment before and after myocardial infarction decreased no reflow and microvascular injury, leading to reduced infiltration of inflammatory cells, reduced infarct size, and improved cardiac function in mice. In diabetic patients receiving empagliflozin after myocardial infarction, perfused boundary region, flow-mediated dilation, and global longitudinal strain were improved.