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http://hdl.handle.net/10773/41269
Title: | Myocardial RNA sequencing reveals new potential therapeutic targets in heart failure with preserved ejection fraction |
Author: | Inácio, José M. Cristo, Fernando Pinheiro, Miguel Vasques-Nóvoa, Francisco Saraiva, Francisca Nunes, Mafalda M. Rosas, Graça Reis, Andreia Coimbra, Rita Oliveira, José Luís Moura, Gabriela Leite-Moreira, Adelino Belo, José António |
Keywords: | Heart failure HFpEF miRNA signature in HFpEF miRNA–mRNA Intercellular communication |
Issue Date: | Aug-2023 |
Publisher: | MDPI |
Abstract: | Heart failure with preserved ejection fraction (HFpEF) represents a global health challenge, with limited therapies proven to enhance patient outcomes. This makes the elucidation of disease mechanisms and the identification of novel potential therapeutic targets a priority. Here, we performed RNA sequencing on ventricular myocardial biopsies from patients with HFpEF, prospecting to discover distinctive transcriptomic signatures. A total of 306 differentially expressed mRNAs (DEG) and 152 differentially expressed microRNAs (DEM) were identified and enriched in several biological processes involved in HF. Moreover, by integrating mRNA and microRNA expression data, we identified five potentially novel miRNA-mRNA relationships in HFpEF: the upregulated hsa-miR-25-3p, hsa-miR-26a-5p, and has-miR4429, targeting HAPLN1; and NPPB mRNA, targeted by hsa-miR-26a-5p and miR-140-3p. Exploring the predicted miRNA-mRNA interactions experimentally, we demonstrated that overexpression of the distinct miRNAs leads to the downregulation of their target genes. Interestingly, we also observed that microRNA signatures display a higher discriminative power to distinguish HFpEF sub-groups over mRNA signatures. Our results offer new mechanistic clues, which can potentially translate into new HFpEF therapies. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/41269 |
DOI: | 10.3390/biomedicines11082131 |
Appears in Collections: | IBIMED - Artigos IEETA - Artigos DCM - Artigos |
Files in This Item:
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biomedicines-11-02131 (1).pdf | 2.44 MB | Adobe PDF | View/Open |
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