Circulating Endothelial Microvesicles with HIV-1 Promote a Proinflammatory Endothelial Cell Phenotype

We have previously reported that circulating endothelial cell derived extracellular microvesicles (EMVs) are elevated in adults living with HIV-1 (ALWH) potentially contributing to HIV-1-related vascular inflammation. Increased vascular inflammation contributes to the increased risk of cardiovascular and cerebrovascular disease in ALWH. The experimental aim of this study was to determine the effect of EMVs isolated from treatment-naïve ALWH on endothelial cell inflammation, in vitro. Twenty-four sedentary, adults were studied: 12 healthy (10M/2F; age 35±2 yr) and 12 treatment naïve ALWH (10M/2F; 35±2 yr; viral load: 7342 copies/mL). All subjects were non-obese, normotensive, normolipidemic and free of overt cardiometabolic disease. Circulating EMV (CD144-PE) number was determined by flow cytometry. Human coronary artery endothelial cells (HCAECs) were cultured and treated with EMVs (CD144-PE) isolated from the healthy adults and treatment naïve ALWH. Circulating EMVs were ~75% higher (P< 0.05) in the treatment naïve ALWH (234±20 EMV/μL) vs healthy (135±13 EMV/μL) adults. EMVs from ALWH induced greater (~20%) release of IL-6 (492.7±94.9 vs 410.7±70.1 pg/mL; P=0.02) from HCAECs compared with EMVs from healthy adults. Intracellular expression of total nuclear factor-kB (NF-kB) p65 (100.0+23.9 vs 112.3+16.4 AU; P=0.16) was not significantly different in cells treated with EMVs from healthy adults and ALWH. However, EMVs from ALWH resulted in ~30% higher expression of p-NF-kB p65 (Ser536; active NF-kB) (58.4+16.1 vs 44.3+11.7 AU; P=0.02). The NF-kB inhibitor, IKK 16, significantly blunted the HIV-related EMV induced production of IL-6 (492.7±94.9 vs 370.6±94.1 pg/mL; P=0.004). IKK 16 had no significant effect on total NF-kB expression (112.3+16.4 vs 92.2±36.4 AU; P=0.10), however, p-NF-kB (Ser536) expression was lower (58.4+16.1 vs 46.5±10.0 AU; P=0.04) in the cells co-treated with EMVs from the ALWH and IKK 1. These results demonstrate, for the first time, HIV-1, independent of traditional risk factors and antiretroviral therapy, is associated with a proinflammatory circulating EMV phenotype. Consistent with greater IL-6 production, cellular NF-kB activation was upregulated in HCAECs treated with EMVs from ALWH. NF-kB is the main transcription factor regulating the production and release IL-6. Circulating EMVs represents a causative factor in HIV-1-related vascular inflammation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.