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, TN, USA., Priest S; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA., Ismael 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, TN, USA., Zhang X; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA., Stolze LK; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA., Sheng Q; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA., Vue Z; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Neikirk K; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Beasley H; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Gabriel C; Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA., Temu T; Division of Pathology, Harvard Medical College, Boston, MA, USA., Gianella S; Division of Infectious Diseases, University of California, San Diego, CA, USA., Mallal S; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia., Koethe JR; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA., Hinton A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Bailin S; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA., Wanjalla CN; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 12. Date of Electronic Publication: 2024 Mar 12.
DOI:	10.1101/2024.03.10.584280
Abstrakt:	Chronic systemic inflammation contributes to a substantially elevated risk of myocardial infarction in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis that contribute to cardiovascular disease. Our objective was to study the effects of plasma from PLWH on endothelial cell (EC) function, with the hypothesis that cytokines and chemokines are major drivers of EC activation. We first broadly phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in adipose tissue in the subcutaneous adipose tissue of 59 PLWH using single cell transcriptomic analysis. We used CellChat to predict cell-cell interactions between ECs and other cells in the adipose tissue and Spearman correlation to measure the association between ECs and plasma cytokines. Finally, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk sequencing to study the direct effects ex-vivo. We observed that arterial and capillary ECs expressed higher interferon and tumor necrosis factor (TNF) receptors. Venous ECs had more interleukin (IL)-1R1 and ACKR1 receptors, and VSMCs had high significant IL-6R expression. CellChat predicted ligand-receptor interactions between adipose tissue immune cells as senders and capillary ECs as recipients in TNF-TNFRSF1A/B interactions. Chemokines expressed largely by capillary ECs were predicted to bind ACKR1 receptors on venous ECs. Beyond the adipose tissue, the proportion of venous ECs and VSMCs were positively plasma IL-6. In ex-vivo experiments, HAECs cultured with plasma-conditioned media from PLWH expressed transcripts that enriched for the TNF-α and reactive oxidative phosphorylation pathways. In conclusion, ECs demonstrate heterogeneity in cytokine and chemokine receptor expression. Further research is needed to fully elucidate the role of cytokines and chemokines in EC dysfunction and to develop effective therapeutic strategies. Competing Interests: Declaration of interests The authors have no competing interests.
Databáze:	MEDLINE
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