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Long-term treated HIV infection is associated with platelet mitochondrial dysfunction
HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNA(pl)) and mitochondri...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973809/ https://www.ncbi.nlm.nih.gov/pubmed/33739024 http://dx.doi.org/10.1038/s41598-021-85775-5 |
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author | van der Heijden, Wouter A. van de Wijer, Lisa Jaeger, Martin Grintjes, Karin Netea, Mihai G. Urbanus, Rolf T. van Crevel, Reinout van den Heuvel, Lambertus P. Brink, Maaike Rodenburg, Richard J. de Groot, Philip G. van der Ven, Andre J. de Mast, Quirijn |
author_facet | van der Heijden, Wouter A. van de Wijer, Lisa Jaeger, Martin Grintjes, Karin Netea, Mihai G. Urbanus, Rolf T. van Crevel, Reinout van den Heuvel, Lambertus P. Brink, Maaike Rodenburg, Richard J. de Groot, Philip G. van der Ven, Andre J. de Mast, Quirijn |
author_sort | van der Heijden, Wouter A. |
collection | PubMed |
description | HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNA(pl)) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function. In a cohort of 208 treated PLHIV and 56 uninfected controls, mtDNA(pl) was quantified, as well as platelet activation, platelet agonist-induced reactivity and inflammation by circulating factors and flow cytometry. In a subgroup of participants, the metabolic activity of platelets was further studied by mitochondrial function tests and the Seahorse Flux Analyzer. PLHIV had significantly lower mtDNA(pl) compared to controls (8.5 copies/platelet (IQR: 7.0–10.7) vs. 12.2 copies/platelet (IQR: 9.5–16.6); p < 0.001), also after correction for age, sex and BMI. Prior zidovudine-use (n = 46) was associated with a trend for lower mtDNA(pl). PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNA(pl) correlated positively with both platelet parameters and correlated negatively with inflammatory marker sCD163. Mitochondrial function tests in a subgroup of participants confirmed the presence of platelet mitochondrial respiration defects. Platelet mitochondrial function is disturbed in PLHIV, which may contribute to platelet dysfunction and subsequent complications. Interventions targeting the preservation of normal platelet mitochondrial function may ultimately prove beneficial for PLHIV. |
format | Online Article Text |
id | pubmed-7973809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79738092021-03-19 Long-term treated HIV infection is associated with platelet mitochondrial dysfunction van der Heijden, Wouter A. van de Wijer, Lisa Jaeger, Martin Grintjes, Karin Netea, Mihai G. Urbanus, Rolf T. van Crevel, Reinout van den Heuvel, Lambertus P. Brink, Maaike Rodenburg, Richard J. de Groot, Philip G. van der Ven, Andre J. de Mast, Quirijn Sci Rep Article HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNA(pl)) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function. In a cohort of 208 treated PLHIV and 56 uninfected controls, mtDNA(pl) was quantified, as well as platelet activation, platelet agonist-induced reactivity and inflammation by circulating factors and flow cytometry. In a subgroup of participants, the metabolic activity of platelets was further studied by mitochondrial function tests and the Seahorse Flux Analyzer. PLHIV had significantly lower mtDNA(pl) compared to controls (8.5 copies/platelet (IQR: 7.0–10.7) vs. 12.2 copies/platelet (IQR: 9.5–16.6); p < 0.001), also after correction for age, sex and BMI. Prior zidovudine-use (n = 46) was associated with a trend for lower mtDNA(pl). PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNA(pl) correlated positively with both platelet parameters and correlated negatively with inflammatory marker sCD163. Mitochondrial function tests in a subgroup of participants confirmed the presence of platelet mitochondrial respiration defects. Platelet mitochondrial function is disturbed in PLHIV, which may contribute to platelet dysfunction and subsequent complications. Interventions targeting the preservation of normal platelet mitochondrial function may ultimately prove beneficial for PLHIV. Nature Publishing Group UK 2021-03-18 /pmc/articles/PMC7973809/ /pubmed/33739024 http://dx.doi.org/10.1038/s41598-021-85775-5 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article van der Heijden, Wouter A. van de Wijer, Lisa Jaeger, Martin Grintjes, Karin Netea, Mihai G. Urbanus, Rolf T. van Crevel, Reinout van den Heuvel, Lambertus P. Brink, Maaike Rodenburg, Richard J. de Groot, Philip G. van der Ven, Andre J. de Mast, Quirijn Long-term treated HIV infection is associated with platelet mitochondrial dysfunction |
title | Long-term treated HIV infection is associated with platelet mitochondrial dysfunction |
title_full | Long-term treated HIV infection is associated with platelet mitochondrial dysfunction |
title_fullStr | Long-term treated HIV infection is associated with platelet mitochondrial dysfunction |
title_full_unstemmed | Long-term treated HIV infection is associated with platelet mitochondrial dysfunction |
title_short | Long-term treated HIV infection is associated with platelet mitochondrial dysfunction |
title_sort | long-term treated hiv infection is associated with platelet mitochondrial dysfunction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973809/ https://www.ncbi.nlm.nih.gov/pubmed/33739024 http://dx.doi.org/10.1038/s41598-021-85775-5 |
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