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RESEARCH PRODUCT

Abacavir Induces Arterial Thrombosis in a Murine Model.

Isabel AndújarMaría Amparo Blanch-ruizSamuel OrdenJuan V. EspluguesM. A. Martínez-cuestaÁNgeles ÁLvarezAna Blas-garciaAinhoa Sánchez-lópezVictor Collado-diaz

subject

0301 basic medicineDrugMaleAnti-HIV Agentsmedia_common.quotation_subject030204 cardiovascular system & hematologyPharmacologyProinflammatory cytokine03 medical and health sciences0302 clinical medicineimmune system diseasesAbacavirmedicineImmunology and AllergyAnimalsRofecoxibmedia_commonMice KnockoutDose-Response Relationship Drugbusiness.industryPurinergic receptorAntagonistvirus diseasesThrombosisPurinergic signallingmedicine.diseaseThrombosisDideoxynucleosidesDisease Models Animal030104 developmental biologyInfectious DiseasesReceptors Purinergic P2X7businessmedicine.drug

description

Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was nonexistent in P2X7 knockout mice. The effects of abacavir were similar to those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects. Conclusion Abacavir promotes arterial thrombosis through interference with purinergic signaling, suggesting a possible biological mechanism for the clinical association of abacavir with cardiovascular diseases.

yearjournalcountryeditionlanguage
2018-01-16The Journal of infectious diseases
10.1093/infdis/jiy001https://pubmed.ncbi.nlm.nih.gov/29346575