Palmitate Stimulates Expression of the von Willebrand Factor and Modulates Toll-like Receptors Level and Activity in Human Umbilical Vein Endothelial Cells (HUVECs).

Autor: Seliga AK; Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, Poland., Zabłocki K; Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, Poland., Bandorowicz-Pikuła J; Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, Poland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Dec 23; Vol. 25 (1). Date of Electronic Publication: 2023 Dec 23.
DOI: 10.3390/ijms25010254
Abstrakt: 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 VWF gene expression, vWF protein maturation, and stimulated vWF secretion. Cardamonin, a Nuclear Factor kappa B (NF-κB) inhibitor, abolished the palmitate effect on VWF 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 TLR6 , CD36 , and TIRAP . 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.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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