Long-term treated HIV infection is associated with platelet mitochondrial dysfunction

Abstract 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 (mtDNApl) and mito...

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Autores principales:	Wouter A. van der Heijden, Lisa van de Wijer, Martin Jaeger, Karin Grintjes, Mihai G. Netea, Rolf T. Urbanus, Reinout van Crevel, Lambertus P. van den Heuvel, Maaike Brink, Richard J. Rodenburg, Philip G. de Groot, Andre J. van der Ven, Quirijn de Mast
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b0bbf380d5ca4357833187a10f35d9b8
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spelling	oai:doaj.org-article:b0bbf380d5ca4357833187a10f35d9b82021-12-02T11:39:47ZLong-term treated HIV infection is associated with platelet mitochondrial dysfunction10.1038/s41598-021-85775-52045-2322https://doaj.org/article/b0bbf380d5ca4357833187a10f35d9b82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85775-5https://doaj.org/toc/2045-2322Abstract 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 (mtDNApl) 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, mtDNApl 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 mtDNApl 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 mtDNApl. PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNApl 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.Wouter A. van der HeijdenLisa van de WijerMartin JaegerKarin GrintjesMihai G. NeteaRolf T. UrbanusReinout van CrevelLambertus P. van den HeuvelMaaike BrinkRichard J. RodenburgPhilip G. de GrootAndre J. van der VenQuirijn de MastNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wouter A. van der Heijden Lisa van de Wijer Martin Jaeger Karin Grintjes Mihai G. Netea Rolf T. Urbanus Reinout van Crevel Lambertus P. van den Heuvel Maaike Brink Richard J. Rodenburg Philip G. de Groot Andre J. van der Ven Quirijn de Mast Long-term treated HIV infection is associated with platelet mitochondrial dysfunction
description	Abstract 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 (mtDNApl) 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, mtDNApl 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 mtDNApl 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 mtDNApl. PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNApl 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	article
author	Wouter A. van der Heijden Lisa van de Wijer Martin Jaeger Karin Grintjes Mihai G. Netea Rolf T. Urbanus Reinout van Crevel Lambertus P. van den Heuvel Maaike Brink Richard J. Rodenburg Philip G. de Groot Andre J. van der Ven Quirijn de Mast
author_facet	Wouter A. van der Heijden Lisa van de Wijer Martin Jaeger Karin Grintjes Mihai G. Netea Rolf T. Urbanus Reinout van Crevel Lambertus P. van den Heuvel Maaike Brink Richard J. Rodenburg Philip G. de Groot Andre J. van der Ven Quirijn de Mast
author_sort	Wouter A. van der Heijden
title	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_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_sort	long-term treated hiv infection is associated with platelet mitochondrial dysfunction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b0bbf380d5ca4357833187a10f35d9b8
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Long-term treated HIV infection is associated with platelet mitochondrial dysfunction

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