Circulating Microparticles Are Elevated in Treated HIV -1 Infection and Are Deleterious to Endothelial Cell Function

Abstract

Background-Circulating microparticles have emerged as biomarkers and effectors of vascular disease. Elevated rates of cardiovascular disease are seen in HIV-1-seropositive individuals. The aims of this study were to determine: (1) if circulating microparticles are elevated in antiretroviral therapy-treated HIV-1-seropositive adults; and (2) the effects of microparticles isolated from antiretroviral therapy-treated HIV-1-seropositive adults on endothelial cell function, in vitro. Methods and Results-Circulating levels of endothelial-, platelet-, monocyte-, and leukocyte-derived microparticles were determined by flow cytometry in plasma from 15 healthy and 15 antiretroviral therapy-treated, virologically suppressed HIV-1-seropositive men. Human umbilical vein endothelial cells were treated with microparticles from individual subjects for 24 hours; thereafter, endothelial cell inflammation, oxidative stress, senescence, and apoptosis were assessed. Circulating concentrations of endothelial-, platelet-, monocyte-, and leukocyte-derived microparticles were significantly higher (approximate to 35%-225%) in the HIV-1-seropositive compared with healthy men. Microparticles from HIV-1-seropositive men induced significantly greater endothelial cell release of interleukin-6 and interleukin-8 (approximate to 20% and approximate to 35%, respectively) and nuclear factor-jB expression while suppressing anti-inflammatory microRNAs (miR-146a and miR-181b). Intracellular reactive oxygen species production and expression of reactive oxygen species-related heat shock protein 70 were both higher in cells treated with microparticles from the HIV-1-seropositive men. In addition, the percentage of senescent cells was significantly higher and sirtuin 1 expression lower in cells treated with HIV-1-related microparticles. Finally, caspase-3 was significantly elevated by microparticles from HIV-1-seropositive men. Conclusions-Circulating concentrations of endothelial-, platelet-, monocyte-, and leukocyte-derived microparticles were higher in antiretroviral therapy-treated HIV-1-seropositive men and adversely affect endothelial cells promoting cellular inflammation, oxidative stress, senescence, and apoptosis. Circulating microparticles may contribute to the vascular risk associated with HIV-1 infection.