Increased Proangiogenic Activity of Mobilized CD34+ Progenitor Cells of Patients With Acute ST-Segment-Elevation Myocardial Infarction: Role of Differential Micro-RNA-378 Expression.

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 and Landmesser, Ulf (2017). Increased Proangiogenic Activity of Mobilized CD34+ Progenitor Cells of Patients With Acute ST-Segment-Elevation Myocardial Infarction: Role of Differential Micro-RNA-378 Expression. Arteriosclerosis, thrombosis, and vascular biology, 37(2), pp. 341-349. Lippincott Williams & Wilkins 10.1161/ATVBAHA.116.308695

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OBJECTIVE

Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. Micro-RNAs (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 is, 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.

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