Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
FISABIO-Fundación Hospital Universitario Dr Peset, Valencia, Spain.
J Infect Dis. 2018 Jun 20;218(2):228-233. doi: 10.1093/infdis/jiy001.
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.
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.
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.
Abacavir promotes arterial thrombosis through interference with purinergic signaling, suggesting a possible biological mechanism for the clinical association of abacavir with cardiovascular diseases.
已知嘌呤能系统是促血栓形成和促炎血管程序的基础，使得阿巴卡韦所表现出的实验作用与血栓形成一致。然而，该药物具有促血栓形成作用的确切证据一直缺乏。
本研究在动脉血栓形成的一种经过良好验证的动物模型中评估了阿巴卡韦的作用。还评估了 ATP-P2X7 受体在药物作用中的作用，并评估和比较了公认的血管损伤剂和其他核苷逆转录酶抑制剂（NRTIs）与阿巴卡韦的作用。
阿巴卡韦剂量依赖性地促进血栓形成。这种作用可被 P2X7 受体拮抗剂逆转，并且在 P2X7 敲除小鼠中不存在。阿巴卡韦的作用与双氯芬酸和罗非昔布相似。其他 NRTIs 没有与血栓形成相关的作用。
阿巴卡韦通过干扰嘌呤能信号促进动脉血栓形成，这表明阿巴卡韦与心血管疾病的临床关联可能存在一种生物学机制。
