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

• Published in: Journal of the American Heart Association Vol. 8; no. 4; p. e011134
• Main Authors: Hijmans, Jamie G., Stockelman, Kelly A., Garcia, Vinicius, Levy, Ma'ayan V., Brewster, L. Madden, Bammert, Tyler D., Greiner, Jared J., Stauffer, Brian L., Connick, Elizabeth, DeSouza, Christopher A.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 19.02.2019; Wiley
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Biomarkers - blood; Cardiovascular Diseases - blood; Cardiovascular Diseases - etiology; Cardiovascular Diseases - physiopathology; Cell-Derived Microparticles - metabolism; Cells, Cultured; endothelial dysfunction; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Female; Flow Cytometry; HIV - immunology; HIV Antibodies - immunology; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV‐1; Humans; inflammation; Male; microparticles; microRNA; Middle Aged; Original Research; Vasodilation - physiology; Young Adult; microRNA; microparticles; HIV‐1; inflammation; endothelial dysfunction
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.118.011134

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 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.