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Cytokine and chemokine receptor profiles in adipose tissue vasculature unravel endothelial cell responses in HIV
Journal article   Open access   Peer reviewed

Cytokine and chemokine receptor profiles in adipose tissue vasculature unravel endothelial cell responses in HIV

Laventa M Obare, Stephen Priest, Anas Ismail, Mona Mashayekhi, Xiuqi Zhang, Lindsey K Stolze, Quanhu Sheng, Kisyua Nthenge, Zer Vue, Kit Neikirk, …
Journal of cellular physiology, Vol.239(11), e31415
2024
DOI: https://doi.org/10.1002/jcp.31415
PMID: 39263801
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Published3.86 MBDownloadView
Open Access CC BY-NC-ND V4.0

Abstract

Adipose Tissue - metabolism Adipose Tissue - pathology Adult Cells, Cultured Cytokines - genetics Cytokines - metabolism Endothelial Cells - metabolism Endothelial Cells - pathology Female Glucose Intolerance - genetics Glucose Intolerance - metabolism Glucose Intolerance - pathology HIV Infections Humans Male Middle Aged Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Myocytes, Smooth Muscle - metabolism Myocytes, Smooth Muscle - pathology Receptors, Chemokine - genetics Receptors, Chemokine - metabolism
Chronic systemic inflammation significantly increases myocardial infarction risk in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis, contributing to cardiovascular disease. We aimed to characterize endothelial cell (EC) chemokines, cytokine, and chemokine receptors of PLWH, hypothesizing that in our cohort, glucose intolerance contributes to their differential expression implicated in endothelial dysfunction. Using single-cell transcriptomic analysis, we phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in subcutaneous adipose tissue of 59 PLWH with and without glucose intolerance. Our results show that arterial and capillary ECs express significantly higher interferon and tumor necrosis factor (TNF) receptors than venous ECs and VSMCs. Venous ECs exhibited more interleukin (IL)1R1 and ACKR1 receptors, and VSMCs showed significant IL6R expression than arterial and capillary ECs. When stratified by group, arterial ECs from PLWH with glucose intolerance expressed significantly higher IL1R1, IL6R, CXCL12, CCL14, and ICAM2 transcripts than arterial ECs from PLWH without diabetes. Of the different vascular cell types studied, arterial ECs as a proportion of all ECs in adipose tissue were positively correlated with plasma fasting blood glucose. In contrast, venous ECs and VSMCs were positively correlated with plasma IL6. To directly assess the effect of plasma from PLWH on endothelial function, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk RNA sequencing. Plasma from PLWH stimulated ECs with the upregulation of genes that enrich for the oxidative phosphorylation and the TNF-α via NFK-β pathways. In conclusion, ECs in PLWH show heterogeneous cytokine and chemokine receptor expression, and arterial ECs were the most influenced by glucose intolerance. Further research must explicate cytokine and chemokine roles in EC dysfunction and identify biomarkers for disease progression and therapeutic response.

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