Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs)
An increased concentration of palmitate in circulation is one of the most harmful factors in obesity. The von Willebrand factor (vWF), a protein involved in haemostasis, is produced and secreted by the vascular endothelium. An increased level of vWF in obese patients is associated with thrombosis an...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/254 |
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| author | Agnieszka K. Seliga Krzysztof Zabłocki Joanna Bandorowicz-Pikuła |
| author_facet | Agnieszka K. Seliga Krzysztof Zabłocki Joanna Bandorowicz-Pikuła |
| author_sort | Agnieszka K. Seliga |
| collection | DOAJ |
| description | An increased concentration of palmitate in circulation is one of the most harmful factors in obesity. The von Willebrand factor (vWF), a protein involved in haemostasis, is produced and secreted by the vascular endothelium. An increased level of vWF in obese patients is associated with thrombosis and cardiovascular disease. The aim of this study was to investigate a palmitate effect on vWF in endothelial cells and understand the mechanisms of palmitate-activated signalling. Human umbilical vein endothelial cells (HUVECs) incubated in the presence of palmitate, exhibited an increased <i>VWF</i> gene expression, vWF protein maturation, and stimulated vWF secretion. Cardamonin, a Nuclear Factor kappa B (NF-κB) inhibitor, abolished the palmitate effect on <i>VWF</i> expression. The inhibition of Toll-like receptor (TLR) 2 with C29 resulted in the TLR4 overactivation in palmitate-treated cells. Palmitate, in the presence of TLR4 inhibitor TAK-242, leads to a higher expression of <i>TLR6</i>, <i>CD36</i>, and <i>TIRAP</i>. The silencing of TLR4 resulted in an increase in TLR2 level and vice versa. The obtained results indicate a potential mechanism of obesity-induced thrombotic complication caused by fatty acid activation of NF-κB signalling and vWF upregulation and help to identify various compensatory mechanisms related to TLR4 signal transduction. |
| first_indexed | 2024-03-08T15:05:25Z |
| format | Article |
| id | doaj.art-80125c8fb90b4bacad14d9876f3cbe17 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:25Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-80125c8fb90b4bacad14d9876f3cbe172024-01-10T14:58:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125125410.3390/ijms25010254Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs)Agnieszka K. Seliga0Krzysztof Zabłocki1Joanna Bandorowicz-Pikuła2Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, PolandLaboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, PolandLaboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, PolandAn increased concentration of palmitate in circulation is one of the most harmful factors in obesity. The von Willebrand factor (vWF), a protein involved in haemostasis, is produced and secreted by the vascular endothelium. An increased level of vWF in obese patients is associated with thrombosis and cardiovascular disease. The aim of this study was to investigate a palmitate effect on vWF in endothelial cells and understand the mechanisms of palmitate-activated signalling. Human umbilical vein endothelial cells (HUVECs) incubated in the presence of palmitate, exhibited an increased <i>VWF</i> gene expression, vWF protein maturation, and stimulated vWF secretion. Cardamonin, a Nuclear Factor kappa B (NF-κB) inhibitor, abolished the palmitate effect on <i>VWF</i> expression. The inhibition of Toll-like receptor (TLR) 2 with C29 resulted in the TLR4 overactivation in palmitate-treated cells. Palmitate, in the presence of TLR4 inhibitor TAK-242, leads to a higher expression of <i>TLR6</i>, <i>CD36</i>, and <i>TIRAP</i>. The silencing of TLR4 resulted in an increase in TLR2 level and vice versa. The obtained results indicate a potential mechanism of obesity-induced thrombotic complication caused by fatty acid activation of NF-κB signalling and vWF upregulation and help to identify various compensatory mechanisms related to TLR4 signal transduction.https://www.mdpi.com/1422-0067/25/1/254endotheliumpalmitatevon Willebrand factorNF-κBTLR2TLR4 |
| spellingShingle | Agnieszka K. Seliga Krzysztof Zabłocki Joanna Bandorowicz-Pikuła Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs) International Journal of Molecular Sciences endothelium palmitate von Willebrand factor NF-κB TLR2 TLR4 |
| title | Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs) |
| title_full | Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs) |
| title_fullStr | Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs) |
| title_full_unstemmed | Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs) |
| title_short | Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs) |
| title_sort | palmitate stimulates expression of the von willebrand factor and modulates toll like receptors level and activity in human umbilical vein endothelial cells huvecs |
| topic | endothelium palmitate von Willebrand factor NF-κB TLR2 TLR4 |
| url | https://www.mdpi.com/1422-0067/25/1/254 |
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