Role of differential microRNA 378 expression in increased pro-angiogenic activity of mobilized CD34+ progenitor cells of patients with acute ST-elevation myocardial infarction:

ABSTRACT: Rationale: Pro-angiogenic effects of mobilised bone-marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. Objective: To determine the differential regulation of angiomiRs, i.e microRNAs regulating neovascularisation, in mobilised CD34+ progenitor cells obtained from patients with an acute ST-segment elevation myocardial infarction (STEMI) as compared to those with stable coronary artery disease (sCAD) or healthy subjects. Methods and Results: CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), sCAD and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased pro-angiogenic activity as compared to CD34+ cells from the other groups. Using a PCR-based miRNA-array and Real-Time PCR validation we identified a profound up-regulation of two known angio-miRs, i.e. miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the pro-angiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in-vitro and in-vivo, whereas let-7b up-regulation in CD34+ cells failed to proof its effect on endothelial cells in-vivo. Conclusion: The present study demonstrates for the first time a significant upregulation of the angiomiRs miR-378 and let-7b in mobilised CD34+ progenitor cells of patients with STEMI. The increased pro-angiogenic 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 microRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53211 | GEO | 2016/11/11

SECONDARY ACCESSION(S): PRJNA231115

REPOSITORIES: GEO