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 (≈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 (≈20% and ≈35%, respectively) and nuclear factor-κB expression while suppressing antiinflammatory 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.
- Endothelial dysfunction
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine