Plasma extracellular vesicles in people living with HIV and type 2 diabetes are related to microbial translocation and cardiovascular risk

Beate Vestad; Tuula A. Nyman; Malene Hove-Skovsgaard; Maria Stensland; Hedda Hoel; Anne Marie Siebke Trøseid; Trude Aspelin; Hans Christian D. Aass; Maija Puhka; Johannes R. Hov; Susanne Dam Nielsen; Reidun Øvstebø; Marius Trøseid

doi:10.1038/s41598-021-01334-y

Plasma extracellular vesicles in people living with HIV and type 2 diabetes are related to microbial translocation and cardiovascular risk

Beate Vestad^*, Tuula A. Nyman, Malene Hove-Skovsgaard, Maria Stensland, Hedda Hoel, Anne Marie Siebke Trøseid, Trude Aspelin, Hans Christian D. Aass, Maija Puhka, Johannes R. Hov, Susanne Dam Nielsen, Reidun Øvstebø, Marius Trøseid

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

6 Citationer (Scopus)

19 Downloads (Pure)

Abstract

HIV and type 2 diabetes (T2D) are both associated with gut microbiota alterations, low-grade endotoxemia and increased cardiovascular risk. We investigated the potential role of plasma extracellular vesicles (EVs) in relation to these processes. Plasma EVs were isolated by size exclusion chromatography in fasting individuals with HIV and T2D (n = 16), T2D only (n = 14), HIV only (n = 20) or healthy controls (n = 19), and characterized by transmission electron microscopy, western blot, nanoparticle tracking analysis and quantitative proteomics. The findings were compared to gut microbiota alterations, lipopolysaccharide levels and cardiovascular risk profile. Individuals with concomitant HIV and T2D had higher plasma EV concentration, which correlated closely with plasma lipopolysaccharides, triglycerides and Framingham score, but not with gut microbiota alterations. Proteomic analyses identified 558 human proteins, largely related to cardiometabolic disease genes and upstream regulation of inflammatory pathways, including IL-6 and IL-1β, as well as 30 bacterial proteins, mostly from lipopolysaccharide-producing Proteobacteria. Our study supports that EVs are related to microbial translocation processes in individuals with HIV and T2D. Their proteomic content suggests a contributing role in low-grade inflammation and cardiovascular risk development. The present approach for exploring gut-host crosstalk can potentially identify novel diagnostic biomarkers and therapeutic targets.

Originalsprog	Engelsk
Artikelnummer	21936
Tidsskrift	Scientific Reports
Vol/bind	11
Udgave nummer	1
Antal sider	11
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-021-01334-y
Status	Udgivet - dec. 2021

Bibliografisk note

Funding Information:
This work was supported by the South-Eastern Norway Regional Health Authority (Grant No. 2016004) and the Norwegian foundation Sonneborn Stiftelse. Mass spectrometry-based proteomic analyses were performed by the Proteomics Core Facility, Department of Immunology, University of Oslo/Oslo University Hospital, which is supported by the Core Facilities program of the South-Eastern Norway Regional Health Authority. This core facility is also a member of the National Network of Advanced Proteomics Infrastructure (NAPI), which is funded by the Research Council of Norway INFRASTRUKTUR-program (Project Number: 295910). Inclusion of study participants and collection of clinical material was supported by Novo Nordisk Foundation, Rigshospitalet University Hospital of Copenhagen, and the Augustinus Foundation. The funders had no role in the study design, data collection or analysis, preparation of the manuscript or decision to submit.

Publisher Copyright:
© 2021, The Author(s).

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Citationsformater

Vestad, B., Nyman, T. A., Hove-Skovsgaard, M., Stensland, M., Hoel, H., Trøseid, A. M. S., Aspelin, T., Aass, H. C. D., Puhka, M., Hov, J. R., Nielsen, S. D., Øvstebø, R., & Trøseid, M. (2021). Plasma extracellular vesicles in people living with HIV and type 2 diabetes are related to microbial translocation and cardiovascular risk. Scientific Reports, 11(1), Artikel 21936. https://doi.org/10.1038/s41598-021-01334-y

Vestad, B, Nyman, TA, Hove-Skovsgaard, M, Stensland, M, Hoel, H, Trøseid, AMS, Aspelin, T, Aass, HCD, Puhka, M, Hov, JR, Nielsen, SD, Øvstebø, R & Trøseid, M 2021, 'Plasma extracellular vesicles in people living with HIV and type 2 diabetes are related to microbial translocation and cardiovascular risk', Scientific Reports, bind 11, nr. 1, 21936. https://doi.org/10.1038/s41598-021-01334-y

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abstract = "HIV and type 2 diabetes (T2D) are both associated with gut microbiota alterations, low-grade endotoxemia and increased cardiovascular risk. We investigated the potential role of plasma extracellular vesicles (EVs) in relation to these processes. Plasma EVs were isolated by size exclusion chromatography in fasting individuals with HIV and T2D (n = 16), T2D only (n = 14), HIV only (n = 20) or healthy controls (n = 19), and characterized by transmission electron microscopy, western blot, nanoparticle tracking analysis and quantitative proteomics. The findings were compared to gut microbiota alterations, lipopolysaccharide levels and cardiovascular risk profile. Individuals with concomitant HIV and T2D had higher plasma EV concentration, which correlated closely with plasma lipopolysaccharides, triglycerides and Framingham score, but not with gut microbiota alterations. Proteomic analyses identified 558 human proteins, largely related to cardiometabolic disease genes and upstream regulation of inflammatory pathways, including IL-6 and IL-1β, as well as 30 bacterial proteins, mostly from lipopolysaccharide-producing Proteobacteria. Our study supports that EVs are related to microbial translocation processes in individuals with HIV and T2D. Their proteomic content suggests a contributing role in low-grade inflammation and cardiovascular risk development. The present approach for exploring gut-host crosstalk can potentially identify novel diagnostic biomarkers and therapeutic targets.",

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