![]() ![]() These adverse effects were greatly reduced when the older NRTIs stavudine, zidovudine (AZT) and didanosine were replaced by the newer NRTIs tenofovir (TDF) and abacavir (ABC). The main mechanism underlying NRTI toxicity is inhibition of mitochondrial DNA polymerase Ī³ and increased oxidative stress, resulting in mitochondrial DNA (mtDNA) depletion 6, 7, 8, and mitochondrial dysfunction at the tissue level 7, 9. Mitochondrial dysfunction is a well-known phenomenon in people living with HIV (PLHIV), which has been linked with the use of nucleoside reverse transcriptase inhibitors (NRTIs) 1, 2, 3, 4, 5. Interventions targeting the preservation of normal platelet mitochondrial function may ultimately prove beneficial for PLHIV. Platelet mitochondrial function is disturbed in PLHIV, which may contribute to platelet dysfunction and subsequent complications. Mitochondrial function tests in a subgroup of participants confirmed the presence of platelet mitochondrial respiration defects. MtDNA pl correlated positively with both platelet parameters and correlated negatively with inflammatory marker sCD163. PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. Prior zidovudine-use (nā=ā46) was associated with a trend for lower mtDNA pl. PLHIV had significantly lower mtDNA pl compared to controls (8.5 copies/platelet (IQR: 7.0ā10.7) vs. In a subgroup of participants, the metabolic activity of platelets was further studied by mitochondrial function tests and the Seahorse Flux Analyzer. 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. Here, we studied platelet mitochondrial DNA content (mtDNA pl) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction.
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