1 research outputs found
Circulating lipoprotein-carried miRNome analysis reveals novel VLDL-enriched microRNAs that strongly correlate with the HDL-microRNA profile
Lipoproteins have been described as microRNAs (miRNAs) carriers. Unfortunately, the bibliography on this topic is scarce and shows a high variability between independent investigations. In addition, the miRNA profiles of the LDL and VLDL fractions have not been completely elucidated. Here, we profiled the human circulating lipoprotein-carried miRNome. Lipoprotein fractions (VLDL, LDL and HDL) were isolated from the serum of healthy subjects by ultracentrifugation and purified by size-exclusion chromatography. A panel of 179 miRNAs commonly expressed in circulation was evaluated in the lipoprotein fractions using quantitative real-time PCR (qPCR) assays. A total of 14, 4 and 24 miRNAs were stably detected in the VLDL, LDL and HDL fractions, respectively. VLDL- and HDL-miRNA signatures were highly correlated (rho 0.814), and miR-16–5p, miR-142–3p, miR-223–3p and miR-451a were among the top 5 expressed miRNAs in both fractions. miR-125a-5p, miR-335–3p and miR-1260a, were detected in all lipoprotein fractions. miR-107 and miR-221–3p were uniquely detected in the VLDL fraction. HDL showed the larger number of specifically detected miRNAs (n = 13). Enrichment in specific miRNA families and genomic clusters was observed for HDL-miRNAs. Two sequence motifs were also detected for this group of miRNAs. Functional enrichment analysis including the miRNA signatures from each lipoprotein fraction suggested a potential role in mechanistic pathways previously associated with cardiovascular disease: fibrosis, senescence, inflammation, immune response, angiogenesis, and cardiomyopathy. Collectively, our results not only support the role of lipoproteins as circulating miRNA carriers but also describe for the first time the role of VLDL as a miRNA transporter.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "Miguel Servet 2020: CP20/00041" and co-funded by the European Union. This work is supported by Instituto de Salud Carlos III (PI16/00471, PI20/00334, PI20/00577 and PI21/01523), co-funded by the European Union, IRBLleida - Fundació Dr. Pifarré, CERCA Programme/Generalitat de Catalunya. NR has received financial support from Ministerio de Ciencia, Innovación y Universidades (PID2019-104367RB-100), and Agencia Estatal de Investigación (AEI/10.13039/501100011033) within the Subprograma Ramón y Cajal (RYC-201722879). CIBERDEM (CB07/08/0016), CIBERES (CB07/06/2008) and CIBERCV (CB16/11/00276) are initiatives of the Instituto de Salud Carlos III