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Circulating lipoprotein-carried miRNome analysis reveals novel VLDL-enriched microRNAs that strongly correlate with the HDL-microRNA profile - 29/04/23

Doi : 10.1016/j.biopha.2023.114623 
Guido Rossi-Herring a, 1, Thalia Belmonte b, c, 1, Andrea Rivas-Urbina d, Sonia Benítez d, e, Noemi Rotllan e, f, Javier Crespo g, Vicenta Llorente-Cortés h, i, j, José Luis Sánchez-Quesada d, e, , 1 , David de Gonzalo-Calvo b, c, , 1
a Emerging Infectious Diseases Program, Center of Health Studies (CHS), Universidad del Valle de Guatemala (UVG), Guatemala City, Guatemala 
b Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain 
c CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain 
d Cardiovascular Biochemistry Group, Institut d′Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain 
e CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain 
f Pathogenesis of Lipid-Related Diseases Group, Institut de Recerca de l′Hospital de Sant Pau-IIB Sant Pau, Barcelona, Spain 
g Institut d′Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain 
h Lipids and Cardiovascular Pathology Group, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain 
i Lipids and Cardiovascular Pathology Group, Institut d′Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain 
j CIBER of Cardiovascular Disease (CIBERCV), Institute of Health Carlos III, Madrid, Spain 

Correspondence to: Cardiovascular Biochemistry Group, Institut d′Investigació Biomèdica Sant Pau (IIB SANT PAU), C/ Sant Quintí 77-79, 08041 Barcelona, Spain.Cardiovascular Biochemistry Group, Institut d′Investigació Biomèdica Sant Pau (IIB SANT PAU)C/ Sant Quintí 77-79Barcelona08041Spain.⁎⁎Correspondence to: Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Avda/ Alcalde Rovira Roure 80, 25198 Lleida, Spain.Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleidaAvda/ Alcalde Rovira Roure 80Lleida25198Spain

Abstract

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.

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Graphical Abstract




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Highlights

Lipoproteins, including VLDL, act as miRNA carriers.
The miRNA profile of VLDL and HDL show high similarity.

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Abbreviations : ApoA-I, ApoB, CAD, Cq, GGE, HF, Lp(a), miRNAs, mRNA, ncRNAs, qPCR, RT, SEC

Keywords : HDL, LDL, Lipoprotein, MicroRNA, VLDL


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© 2023  The Authors. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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