| Autor: |
Chun Yi Ng, Khang Leng Lee, Mark D. Muthiah, Kan-Xing Wu, Florence W. J. Chioh, Konstanze Tan, Gwyneth S. T. Soon, Asim Shabbir, Wai Mun Loo, Zun Siong Low, Qingfeng Chen, Nguan Soon Tan, Huck Hui Ng, Yock Young Dan, Christine Cheung |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
The top cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, the mechanisms of NAFLD-associated vasculopathy remain understudied. We developed blood outgrowth endothelial cell (BOEC) models from NAFLD and healthy subjects. NAFLD BOECs exhibited global transcriptional upregulation of chemokine hallmarks and human leukocyte antigens. In mouse models of diet-induced NAFLD, we further confirmed enhanced endothelial expressions of CXCL12 in the aortas and liver vasculatures. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification and potentially T-helper type 1 inflammation in NAFLD patients. Functionally, interference of the CXCL12-CXCR4 axis by small molecule AMD3100 selectively modulated the chemotaxis of patient-derived CD4+ T cells and natural killer cells towards NAFLD BOECs, restoring endothelial barrier integrity. Clinically, we detected three folds more circulating damaged endothelial cells in NAFLD patients than healthy controls. Our work provides insights for modulation of interactions with effector immune subsets to mitigate endothelial injury in NAFLD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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