In vivo platelet activation and platelet hyperreactivity in abacavir-treated HIV-infected patients
| Autor: | Silvia Giannini, Valentina Conti, Daniela Francisci, Franco Baldelli, Paolo Gresele, Stefano Bonora, A. M. Mezzasoma, Lisa Malincarne, Giuseppe Guglielmini, Barbara Belfiori, Manuela Sebastiano, Emanuela Falcinelli, Eleonora Petito |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
0301 basic medicine
Male adverse effects/analogs /&/ derivatives Platelet Aggregation Adenine adverse effects/analogs /&/ derivatives Adult Anti-HIV Agents adverse effects/blood Blood Platelets drug effects/metabolism CD40 Ligand Case-Control Studies Cyclic GMP blood Deoxyguanine Nucleotides adverse effects/blood Dideoxynucleosides adverse effects/blood Female HIV Infections blood/drug therapy Humans Male Middle Aged Nitric Oxide blood Organophosphonates adverse effects P-Selectin blood Phospholipases A2 Secretory blood Platelet Activation drug effects Platelet Aggregation drug effects Retrospective Studies HIV Infections 030204 cardiovascular system & hematology Pharmacology chemistry.chemical_compound 0302 clinical medicine Platelet Cyclic GMP medicine.diagnostic_test biology Deoxyguanine Nucleotides Hematology Middle Aged P-Selectin Female adverse effects/blood Adult Blood Platelets Anti-HIV Agents CD40 Ligand Organophosphonates Nitric Oxide Flow cytometry Nitric oxide 03 medical and health sciences In vivo blood medicine Humans Platelet activation Phospholipases A2 Secretory Tenofovir Retrospective Studies CD40 business.industry Platelet Activation 030112 virology In vitro Dideoxynucleosides Phospholipases A2 chemistry Case-Control Studies drug effects biology.protein adverse effects business drug effects/metabolism blood/drug therapy Ex vivo |
| Popis: | SummaryAbacavir (ABC) has been associated with ischaemic cardiovascular events in HIV-infected patients, but the pathogenic mechanisms are unknown. Aim of our study was to assess whether ABC induces in vivo platelet activation and ex vivo platelet hyper-reactivity. In a retrospective, case-control study, in vivo platelet activation markers were measured in 69 HIV-infected patients, before starting therapy and after 6–12 months of either ABC (n=35) or tenofovir (TDF) (n=34), and compared with those from 20 untreated HIV-infected patients. A subgroup of patients was restudied after 28–34 months for ex vivo platelet reactivity. In vivo platelet activation markers were assessed by ELISA or flow cytometry, ex vivo platelet reactivity by light transmission aggregometry (LTA) and PFA-100®. The in vitro effects of the ABC metabolite, carbovir triphosphate, on aggregation and intra-platelet cGMP were also studied. sPLA2, sPsel and sGPV increased significantly 6–12 months after the beginning of ABC, but not of TDF or of no treatment. Ex vivo platelet function studies showed enhanced LTA, shorter PFA-100® C/ADP closure time and enhanced platelet expression of P-sel and CD40L in the ABC group. The intake of ABC blunted the increase of intraplatelet cGMP induced by nitric oxide (NO) and acutely enhanced collagen-induced aggregation. Preincubation of control platelets with carbovir triphosphate in vitro enhanced platelet aggregation and blunted NO-induced cGMP elevation. In conclusion, treatment with ABC enhances in vivo platelet activation and induces platelet hyperreactivity by blunting the inhibitory effects of NO on platelets. These effects may lead to an increase of ischaemic cardiovascular events. |
| Databáze: | OpenAIRE |
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