Abstract
People with HIV (PWH) experience endothelial dysfunction (ED) that is aggravated by chronic inflammation and microbial translocation across a damaged gut barrier. Although this paradigm is well-described, downstream pathways that terminate in endothelial dysfunction are only partially understood. This study found increased expression of granulocyte macrophage colony stimulating factor (GM-CSF), toll-like receptor-4 (TLR4), and myeloperoxidase in the aortic endothelium of PWH compared to those without HIV. Bacteria-derived lipopolysaccharide (LPS) heightened glucose uptake and induced GM-CSF expression in primary human endothelial cells. Exposure to sodium-glucose cotransporter-2 (SGLT2) inhibitors reduced glucose uptake, GM-CSF release, and ED in LPS-activated endothelial cells ex vivo, and PWH treated with SGLT2 inhibitors for diabetes had significantly lower plasma GM-CSF levels than non-diabetic PWH not on this medication. The findings suggest that microbial products trigger glucose uptake and GM-CSF expression in the endothelium, contributing to localized inflammation in PWH. Modifying this altered state could offer therapeutic benefits.