Circulating Microparticles Are Elevated in Treated HIV -1 Infection and Are Deleterious to Endothelial Cell Function
AuthorHijmans, Jamie G
Stockelman, Kelly A
Levy, Ma'ayan V
Brewster, L Madden
Bammert, Tyler D
Greiner, Jared J
Stauffer, Brian L
DeSouza, Christopher A
AffiliationUniv Arizona, Div Infect Dis
MetadataShow full item record
CitationHijmans, J. G., Stockelman, K. A., Garcia, V., Levy, M. A. V., Brewster, L. M., Bammert, T. D., ... & DeSouza, C. A. (2019). Circulating Microparticles Are Elevated in Treated HIV‐1 Infection and Are Deleterious to Endothelial Cell Function. Journal of the American Heart Association, 8(4), e011134.
RightsCopyright © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License.
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AbstractBackground-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.
NoteOpen Access Journal
VersionFinal published version
SponsorsNational Institutes of Health (NIH) [HL131458, HL135598]; NIH/National Center for Advancing Translational Sciences [UL1 TR001082]
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