Effects of abacavir on the vascular and platelet activities

Abstract

Abacavir is an antiviral nucleoside analogue effectively used to treat HIV infection. However, a study showed that the use of abacavir significantly increased the risks of stroke and myocardial infraction. We sought to investigate the effects of abacavir on vascular and platelet activities so as to understand the underlying mechanisms. Sprague-Dawley rats (330-350 g) were fed with abacavir (16 mg/kg/day, equivalent to the clinical dosage on human) for 28 days by gastric gavage. Isometric tensions of basilar arteries were measured. Aorta mRNA and proteins expressions of various factors related to endothelial function and inflammation were measured by RT-PCR and Western blotting, respectively. To measure the effect of abacavir on platelet activation, the plasma levels of CD40L, a platelet-derived factor which is released upon platelet activation, were measured by ELISA kit. Our results showed that abacavir treatment did not affect the maximum relaxation response of basilar artery. Besides, there were no significant change in the mRNA and protein expression levels of eNOS, COX-1, COX-2 and ICAM-1 in aorta after abacavir treatment. However, a higher plasma level of CD40L was detected in the abacavir-treated group. It is suggested that abacavir does not affect vascular contractility nor induced endothelial inflammation. However, abacavir upregulates the platelet activity, which will theoretically increase the chance of developing thrombosis. This may be a possible explanation for the higher risk of cardiovascular events in patients receiving abacavir treatment.