Abacavir induces platelet-endothelium interactions by interfering with purinergic signalling: A step from inflammation to thrombosis

Antiviral Res. 2017 May;141:179-185. doi: 10.1016/j.antiviral.2017.03.001. Epub 2017 Mar 2.


The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway. The effects of ABC on platelet aggregation and platelet-endothelium interactions were evaluated, respectively, with an aggregometer and a flow chamber system that reproduced conditions in vivo. The role of adhesion molecules and purinergic receptors in endothelial and platelet populations was assessed by selective pre-incubation with specific antagonists and antibodies. ABC and carbovir triphosphate (CBT) levels were evaluated by HPLC. The results showed that ABC promoted the adherence of platelets to endothelial cells, a crucial step for the formation of thrombi. This was not a consequence of a direct effect of ABC on platelets, but resulted from activation of the endothelium via purinergic ATP-P2X7 receptors, which subsequently triggered an interplay between P-selectin and ICAM-1 on endothelial cells with constitutively expressed GPIIb/IIIa and GPIbα on platelets. ABC did not induce platelet activation (P-selectin expression or Ca2+ mobilization) or aggregation, even at high concentrations. CBT levels in endothelial cells were lower than those required to induce platelet-endothelium interactions. Thus, ABC interference with endothelial purinergic signalling leads to platelet recruitment. This highlights the endothelium as the main cell target of ABC in this interaction, which is in line with previous experimental evidence that ABC induces manifestations of vascular inflammation.

Keywords: Abacavir; Cardiovascular diseases; NRTIs; Platelet-endothelium interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacology*
  • Blood Platelets / drug effects*
  • Blood Platelets / physiology
  • Cardiovascular Diseases / etiology
  • Deoxyguanine Nucleotides / analysis
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / pharmacology*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Humans
  • Inflammation
  • Intercellular Adhesion Molecule-1 / physiology
  • P-Selectin / physiology
  • Platelet Activation / drug effects
  • Platelet Adhesiveness / drug effects*
  • Platelet Aggregation / drug effects*
  • Purines / metabolism*
  • Signal Transduction / drug effects
  • Thrombosis / etiology


  • Anti-HIV Agents
  • Deoxyguanine Nucleotides
  • Dideoxynucleosides
  • ICAM1 protein, human
  • P-Selectin
  • Purines
  • SELP protein, human
  • carbovir triphosphate
  • Intercellular Adhesion Molecule-1
  • abacavir