Christian Templin1, Julia Volkmann1, Maximilian Y. Emmert1, Pavani Mocharla1, Maja Müller1, Nicolle Kränkel1, Jelena R. Ghadri1, Martin Meyer1, Beata Styp‐Rekowska1, Sylvie Briand1, Roland Klingenberg1, Miłosz Jaguszewski1, Christian M. Matter1, Valentin Djonov1, François Mach1, Stephan Windecker1, Simon P. Hoerstrup1, Thomas Thum1, Thomas F. Lüscher1, Ulf Landmesser1
1From 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...
Tóm tắt
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.
