Platelet-Derived MicroRNAs Regulate Cardiac Remodeling After Myocardial Ischemia

作者：Jan Philipp Schütte, Mailin-Christin Manke, Katherina Hemmen, Patrick Münzer, Barbara Francisca Schörg, Gustavo Campos Ramos, Michaela Pogoda, Valerie Dicenta, Sabrina H. L. Hoffmann, Jürgen Pinnecker, Ferdinand Kollotzek, Monika Zdanytė, Karin Anne Lydia Mueller, Yogesh Singh, Andreas F. Mack, Bernd J. Pichler, Florian J.W. Lang, Bernhard Nieswandt, Meinrad Gawaz, Katrin Gertrud Heinze, Nicolas Casadei, Oliver Borst · 发表于：Circulation Research · 年份：2023 · DOI：10.1161/circresaha.122.322459 · 被引用次数：60 · 研究领域：MicroRNA in disease regulation、Cardiac Fibrosis and Remodeling、Extracellular vesicles in disease

Background: Platelets can infiltrate ischemic myocardium and are increasingly recognized as critical regulators of inflammatory processes during myocardial ischemia and reperfusion (I/R). Platelets contain a broad repertoire of microRNAs (miRNAs), which, under certain conditions such as myocardial ischemia, may be transferred to surrounding cells or released into the microenvironment. Recent studies could demonstrate that platelets contribute substantially to the circulating miRNA pool holding the potential for so far undiscovered regulatory functions. The present study aimed to determine the role of platelet-derived miRNAs in myocardial injury and repair following myocardial I/R. Methods: In vivo model of myocardial I/R, multimodal in vivo and ex vivo imaging approaches (light-sheet fluorescence microscopy, positron emission tomography and magnetic resonance imaging, speckle-tracking echocardiography) of myocardial inflammation and remodeling, and next-generation deep sequencing analysis of platelet miRNA expression. Results: In mice with a megakaryocyte/platelet-specific knockout of pre-miRNA processing ribonuclease Dicer , the present study discloses a key role of platelet-derived miRNAs in the tightly regulated cellular processes orchestrating left ventricular remodeling after myocardial I/R following transient left coronary artery ligation. Disruption of the miRNA processing machinery in platelets by deletion of Dicer resulted in increased myocardial inflammation, impair...