Identification of miRNA-497 and miRNA-27b-5p as potential diagnostic markers of cardiac fibrosis
| Autor: | A Maryam, B Reilly-O'donnell, R Tikhomirov, Simona Greco, Carla Lucarelli, Fabio Martelli, Julia Gorelik, P Leszek, P Srivastava, Giuseppe Faggian, Lorenzo Menicanti, G Zacagnini, Costanza Emanueli |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | European Heart Journal. 42 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehab724.3344 |
| Popis: | Background Cardiac fibrosis is associated with inflammation and extracellular matrix (ECM) accumulation. A pro-fibrotic cytokine, IL11 induces cardiac fibroblasts conversion to myofibroblasts expressing α-smooth muscle actin (α-SMA) and ECM. MicroRNAs (miRNAs) are a class of small non-coding RNAs which participate in regulation of gene expression; Although mainly intracellular, miRNAs can be released into the blood stream where they can be readily detected. Purpose To screen miRNAs upregulated following IL11 triggered conversion of rat cardiac fibroblasts into myofibroblasts. To validate these miRNAs as potential diagnostic biomarkers of cardiac fibrosis by testing their level in blood plasma and septum of aortic valve stenosis (AVS) patients. Methods and results With a bioinformatical approach (Figure 1), we predicted miRNAs which can target proteins involved in TGFβ and IL-11 pathways of fibrosis progression. Of a vast number of miRNAs, we identified 7 strong candidates. After qPCR validation, we found miRNA-27b-5p and miRNA-497 to be significantly upregulated in rat cardiac fibroblasts treated by IL11 (5 ng/ul) but not TGFβ1 (100 ng/ul), values are 2–ΔΔCt: (3±1.5) and (5.2±2.2) (p-value Conclusions We found miRNA-497 and miRNA-27b-5p to be pro-fibrotic in rat fibroblasts. Importantly, we found both miRNAs to be up-regulated in the peripheral blood of AVS patients. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Roman Tikhomirov PhD studentship is supported by a fellowship from the University of Verona, ItalyEEU-Cardiac RNA cost action CA17129 |
| Databáze: | OpenAIRE |
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