Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease

Abstract

Objective People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes up-regulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD. Methods Participants with >75th percentile (n=15) and <25th percentile (n=15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry. Results Intermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, p=0.024) (66.4% vs. 48.5%, p=0.031) and CD38 (339 MFI vs. 211 MFI, p=0.002) (10.5% vs. 3.8%, p=0.0002) compared to women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, non-classical monocytes, CD4+ and CD8+ T lymphocytes. Conclusion GLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.

Immunometabolic and Lipidomic Markers Associated With the Frailty Index and Quality of Life in Aging HIV+ Men on Antiretroviral Therapy

“…We have previously demonstrated that Glut1 expression is up-regulated in monocytes from HIV-infected compared to uninfected individuals, even after a mean of 9.3 years of antiretroviral therapy ( Palmer et al, 2014a ). Further, expression of Glut1 is elevated on the intermediate subset of monocytes from HIV-infected women with subclinical cardiovascular disease, supporting a possible role for monocyte glucose metabolic reprogramming in the pathogenesis of non-AIDS comorbidities ( Butterfield et al, 2017 ). Our study found an association between frailty and increased Glut1 expression on the total monocyte population, which marks activation of glycolysis.…”

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

“…In addition, Ixolaris treatment significantly lowered both CD80 expression in chronically infected PTMs (P=0.004, Figure 6G) and CD86 expression in both acutely and chronically infected PTMs (P=0.03, Figure 6H), compared with the untreated controls. To further validate the reduction of monocyte activation induced by Ixolaris treatment, we measured Glut-1 expression on CD14 + monocytes, an important monocyte activation marker (43-45). Ixolaris-treated animals showed a significantly reduced Glut-1 expression following SIV infection, compared to untreated controls (P=0.001, Figure 6I).…”

Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging

“…Analysis of monocytes from HIV-infected participants enrolled in the Women’s Interagency HIV Study showed that the frequency of circulating Glut1-expressing intermediate monocytes is significantly elevated in those with subclinical cardiovascular disease 10 . Furthermore, in a group of aging HIV + men on suppressive combined ART, frailty (evaluated using the Frailty Index) was associated with Glut1 expression on total monocytes 87 .…”