Increased Proangiogenic Activity of Mobilized CD34 + Progenitor Cells of Patients With Acute ST-Segment–Elevation Myocardial Infarction Role of Differential MicroRNA-378 Expression

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 37; no. 2; pp. 341 - 349
• Main Authors: Templin, Christian, Volkmann, Julia, Emmert, Maximilian Y., Mocharla, Pavani, Müller, Maja, Kraenkel, Nicolle, Ghadri, Jelena-R., Meyer, Martin, Styp-Rekowska, Beata, Briand, Sylvie, Klingenberg, Roland, Jaguszewski, Milosz, Matter, Christian M., Djonov, Valentin, Mach, Francois, Windecker, Stephan, Hoerstrup, Simon P., Thum, Thomas, Lüscher, Thomas F., Landmesser, Ulf
• Format: Journal Article
• Language: English
• Published: United States 01.02.2017
• Subjects: Aged; Animals; Antigens, CD34 - metabolism; Case-Control Studies; Cell Movement; Cell Proliferation; Cells, Cultured; Chick Embryo; Coculture Techniques; Endothelial Progenitor Cells - metabolism; Endothelial Progenitor Cells - pathology; Endothelial Progenitor Cells - transplantation; Female; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Male; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Neovascularization, Physiologic; Paracrine Communication; Signal Transduction; ST Elevation Myocardial Infarction - genetics; ST Elevation Myocardial Infarction - metabolism; ST Elevation Myocardial Infarction - pathology; ST Elevation Myocardial Infarction - physiopathology; Time Factors; Transfection; Up-Regulation; coronary artery disease; microRNAs; endothelial cells; myocardial infarction; real-time polymerase chain reaction
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.116.308695

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. 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. 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.