1. Long-term treated HIV infection is associated with platelet mitochondrial dysfunction
- Author
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Lisa Van de Wijer, Quirijn de Mast, Philip G. de Groot, Reinout van Crevel, Maaike Brink, Wouter A. van der Heijden, Lambertus P. van den Heuvel, Karin J. T. Grintjes, Mihai G. Netea, Rolf T. Urbanus, Richard J. Rodenburg, André J. A. M. van der Ven, and Martin Jaeger
- Subjects
Male ,0301 basic medicine ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,HIV Infections ,0302 clinical medicine ,Platelet ,Prospective Studies ,030212 general & internal medicine ,Netherlands ,Multidisciplinary ,medicine.diagnostic_test ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Middle Aged ,Viral Load ,Thrombosis ,Mitochondria ,Cardiovascular diseases ,Treatment Outcome ,Medicine ,Female ,medicine.symptom ,Zidovudine ,Adult ,Blood Platelets ,Mitochondrial DNA ,medicine.medical_specialty ,Anti-HIV Agents ,Science ,Inflammation ,DNA, Mitochondrial ,Article ,Flow cytometry ,03 medical and health sciences ,Medical research ,Oxygen Consumption ,Internal medicine ,medicine ,Humans ,Platelet activation ,Mean platelet volume ,business.industry ,Platelet Activation ,medicine.disease ,Cross-Sectional Studies ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,030104 developmental biology ,Endocrinology ,Case-Control Studies ,HIV-1 ,business ,Ex vivo - 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 pl. 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.
- Published
- 2021