Ritonavir incrementa la expresión de CD36 y ABCA1 en macrófagos THP-1

Ritonavir, a protease inhibitor used in highly active antiretroviral therapy (HAART) for HIV-1 infection, is associated with an increased risk of premature atherosclerosis. It has been proposed that ritonavir facilitates foam cell formation from macrophages, but conflicting results on the effect of this drug on CD36 scavenger receptor expression in monocytes and macrophages have been published. Our results show that ritonavir exposure at concentrations within the therapeutic range cause an increase in CD36 protein and mRNA levels in differentiated THP-1 macrophages, but not in monocytes from the same cell line. Protein kinase C (PKC) activation by the differentiating agent PMA and subsequent peroxisome proliferatoractivated receptor-γ (PPARγ) activation could account for these differences. This mechanism could also explain the increase in ABCA1 expression found in our study, but not the decrease in SR-BI protein, which does not seem to be a transcriptional effect. Finally, PPARγ and CD36 up-regulation by ritonavir are not related to an increase in levels of mature SREBP1.