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Increased proangiogenic activity of mobilized CD34$^+$ progenitor cells of patients with acute ST-segment-elevation myocardial infarction: role of differential MicroRNA-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; Landmesser, Ulf (2017). Increased proangiogenic activity of mobilized CD34$^+$ progenitor cells of patients with acute ST-segment-elevation myocardial infarction: role of differential MicroRNA-378 expression. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(2):341-349.

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 withCD34$^+$ 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.

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 withCD34$^+$ 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:February 2017
Deposited On:03 Feb 2017 09:25
Last Modified:09 Feb 2017 09:41
Publisher:Lippincott Williams & Wilkins
ISSN:1079-5642
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/ATVBAHA.116.308695
PubMed ID:28062497

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