Profiling plasma‐extracellular vesicle proteins and microRNAs in diabetes onset in middle‐aged male participants in the ELSA‐Brasil study

We measured plasma‐derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle‐aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brazil). Mass spectro...

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Published in:	Physiological reports Vol. 9; no. 3; pp. e14731 - n/a
Main Authors:	Masi, Laureane N., Lotufo, Paulo A., Ferreira, Frederico M., Rodrigues, Alice C., Serdan, Tamires D. A., Souza‐Siqueira, Talita, Braga, Aécio A., Saldarriaga, Magda E. G., Alba‐Loureiro, Tatiana C., Borges, Fernanda T., Cury, Diego P., Hirata, Mario H., Gorjão, Renata, Pithon‐Curi, Tania C., Lottenberg, Simão A., Fedeli, Ligia M. G., Nakaya, Helder T. I., Bensenor, Isabela J. M., Curi, Rui, Hirabara, Sandro M.
Format:	Journal Article
Language:	English
Published:	United States John Wiley & Sons, Inc 01-02-2021 John Wiley and Sons Inc Wiley
Subjects:	Biochemical analysis Biomarkers Diabetes Diabetes mellitus Disease epigenetics Estrogens Extracellular vesicles Ferritin Gene expression Glucose glucose intolerance Hemoglobin Hormone replacement therapy Hyperglycemia Immune response Investigations Lipids Mass spectroscopy Metabolism MicroRNAs Microscopy miRNA Mitochondrial DNA Original Physiology Plasma Proteins proteomic Brazil glucose intolerance hyperglycemia proteomic epigenetics
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Summary:	We measured plasma‐derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle‐aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brazil). Mass spectrometry revealed decreased IGHG‐1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR‐141‐3p and downregulation of miR‐324‐5p and ‐376c‐3p compared with the NG and GI groups. The DM and GI groups showed increased miR‐26b‐5p expression compared with that in the NG group. The DM group showed decreased miR‐374b‐5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.
Bibliography:	Funding information We thank the following sources of financial support: Sao Paulo State Research Foundation–FAPESP (2014/21447‐6; 2015/12728‐4; 2017/03707‐9; 2018/00998‐5; 2019/25892‐8), National Council for Scientific and Technological Development–CNPq (457358/2013‐0; 303574/2015‐1; 312018/2018‐5), Coordination for the Improvement of Higher Education Personnel–CAPES (88881.068515/2014‐01; 88881.170862/2018‐01), and Dean of Postgraduate and Research/Cruzeiro do Sul–PRPGP/CS (0708/2018). The ELSA‐Brasil baseline study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science and Technology (Financiadora de Estudos e Projetos and CNPq National Research Council) (grants 01 06 0010.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 0106 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ). ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	2051-817X
DOI:	10.14814/phy2.14731