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

Autor: Obare LM; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Priest S; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Ismail A; Department of Radiology, National Postgraduate Medical College of Nigeria, Lagos, Nigeria., Mashayekhi M; Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Zhang X; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Stolze LK; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Sheng Q; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Nthenge K; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Vue Z; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Neikirk K; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Beasley HK; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Gabriel C; Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Temu T; Division of Pathology, Harvard Medical College, Boston, Massachusetts, USA., Gianella S; Division of Infectious Diseases and Global Public Health, University of California, San Diego, California, USA., Mallal SA; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia., Koethe JR; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA., Hinton A Jr; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Bailin SS; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Wanjalla CN; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2024 Nov; Vol. 239 (11), pp. e31415. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1002/jcp.31415
Abstrakt: 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.
(© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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