Christian Templin1, Julia Volkmann2, Maximilian Y Emmert2, Pavani Mocharla2, Maja Müller2, Nicolle Kraenkel2, Jelena-R Ghadri2, Martin Meyer2, Beata Styp-Rekowska2, Sylvie Briand2, Roland Klingenberg2, Milosz Jaguszewski2, Christian M Matter2, Valentin Djonov2, Francois Mach2, Stephan Windecker2, Simon P Hoerstrup2, Thomas Thum2, Thomas F Lüscher2, Ulf Landmesser2. 1. From the Department of Cardiology, University Heart Center (C.T., P.M., M.M., J.-R.G., M.J., C.M.M., T.F.L.), Department of Cardiovascular Surgery, Department of Surgical Research (M.Y.E., S.P.H.), University Hospital Zurich, Switzerland; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Germany (J.V.); Department of Cardiology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany (N.K., U.L.); Institute of Anatomy, University of Berne, Switzerland (B.S.-R., V.D.); Division of Cardiology, Kantonsspital Frauenfeld, Switzerland (M.M.); Division of Cardiology, Kerckhoff Klinik, Bad Nauheim, Germany (R.K.); Center for Molecular Cardiology, Schlieren Campus and Zurich Center of Integrative Human Physiology (ZIHP), University of Zurich, Switzerland (S.B., T.F.L.); First Department of Cardiology, Medical University of Gdansk, Poland (M.J.); Department of Cardiology, University of Geneva, Switzerland (F.M.); Department of Cardiology, University Hospital Bern, Switzerland (S.W.); Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany (T.T.); and National Heart and Lung Institute, Imperial College London, United Kingdom (T.T.). Christian.Templin@usz.ch. 2. From the Department of Cardiology, University Heart Center (C.T., P.M., M.M., J.-R.G., M.J., C.M.M., T.F.L.), Department of Cardiovascular Surgery, Department of Surgical Research (M.Y.E., S.P.H.), University Hospital Zurich, Switzerland; Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Germany (J.V.); Department of Cardiology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany (N.K., U.L.); Institute of Anatomy, University of Berne, Switzerland (B.S.-R., V.D.); Division of Cardiology, Kantonsspital Frauenfeld, Switzerland (M.M.); Division of Cardiology, Kerckhoff Klinik, Bad Nauheim, Germany (R.K.); Center for Molecular Cardiology, Schlieren Campus and Zurich Center of Integrative Human Physiology (ZIHP), University of Zurich, Switzerland (S.B., T.F.L.); First Department of Cardiology, Medical University of Gdansk, Poland (M.J.); Department of Cardiology, University of Geneva, Switzerland (F.M.); Department of Cardiology, University Hospital Bern, Switzerland (S.W.); Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany (T.T.); and National Heart and Lung Institute, Imperial College London, United Kingdom (T.T.).
Abstract
OBJECTIVE: Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34+ progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects. APPROACH AND RESULTS: CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared with CD34+ cells from the other groups. Using a polymerase chain reaction-based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34+ cells failed to proof its effect on endothelial cells in vivo. CONCLUSIONS: The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34+ progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34+ progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.
OBJECTIVE: Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34+ progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects. APPROACH AND RESULTS: CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared with CD34+ cells from the other groups. Using a polymerase chain reaction-based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34+ cells failed to proof its effect on endothelial cells in vivo. CONCLUSIONS: The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34+ progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34+ progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.
Authors: Jan Fiedler; Andrew H Baker; Stefanie Dimmeler; Stephane Heymans; Manuel Mayr; Thomas Thum Journal: Cardiovasc Res Date: 2018-08-01 Impact factor: 10.787
Authors: Rian Q Landers-Ramos; Ryan M Sapp; Daniel D Shill; James M Hagberg; Steven J Prior Journal: Compr Physiol Date: 2019-03-14 Impact factor: 8.915
Authors: David de Gonzalo-Calvo; Germán Cediel; Christian Bär; Julio Núñez; Elena Revuelta-Lopez; Josep Gavara; César Ríos-Navarro; Vicenta Llorente-Cortes; Vicente Bodí; Thomas Thum; Antoni Bayes-Genis Journal: Sci Rep Date: 2018-10-11 Impact factor: 4.379