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oai:riuma.uma.es:10630/316072026-02-03T10:54:05Zcom_10630_2254col_10630_37953

Inhibition of Endothelial Inflammatory Response by HT-C6, a Hydroxytyrosol Alkyl Ether Derivative. Marrero Capitán, Ana Dácil Castilla, Laura Bernal, Manuel Manrique-Poyato, María Inmaculada Posligua-García, Joel Moya-Utrera, Federico Porras Alcalá, Cristina Espartero Sánchez, José Luis Sarabia-García, Francisco Ramón Rodríguez-Quesada, Ana María Medina-Torres, Miguel Ángel Martínez-Póveda, Beatriz Amparo Antiangiogénicos Arterias - Enfermedades Aceite de oliva Hydroxytyrosol Hydroxytyrosol derivatives; Inflammatory response Endothelial cells NF-KB HT-C6 Antioxidant Atherosclerosis Hydroxytyrosol (HT) is a bioactive phenolic compound naturally present in olives and extra virgin olive oil (EVOO) which is described as an antioxidant, antitumoral and antiangiogenic molecule. Previous studies of semi-synthetic HT-derivatives presented the hydroxytyrosyl alkyl ether HT-C6 as one of the most potent derivatives studied in the context of antioxidant, anti-platelet and antiangiogenic assays, but its direct effect on inflammation was not reported. In this work, we use RT-qPCR measure of gene expression, protein analysis by Western-blot and immunofluorescence techniques, adhesion and migration functional assays and single-cell monitoring of reactive oxygen species (ROS) in order to explore in vitro the ability of HT-C6 to interfere in the inflammatory response of endothelial cells (ECs). Our results showed that HT-C6 strongly reduces the TNF- -induced expression of vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule 1 (ICAM1), E-selectin (SELE), C-C motif chemokine ligand 2 and 5 (CCL2 and CCL5) in HUVECs, impairing the chemotactic and adhesion potential of these cells towards THP-1 monocytes in vitro. In this work, we define a mechanism of action underlying the anti-inflammatory effect of HT-C6, which involves the abrogation of nuclear factor kappa B (NF- B) pathway activation in ECs. These results, together with the ability of HT-C6 to reduce ROS formation in ECs, point to this compound as a promising HT-derivative to be tested in the treatment of atherosclerosis. Partial funding for open access charge: Universidad de Málaga 2024-06-13T11:37:57Z 2024-06-13T11:37:57Z 2023-07-28 journal article VoR Marrero, A. D., Castilla, L., Bernal, M., Manrique, I., Posligua-García, J. D., Moya-Utrera, F., Porras-Alcalá, C., Espartero, J. L., Sarabia, F., Quesada, A. R., Medina, M. Á., & Martínez-Poveda, B. (2023). Inhibition of Endothelial Inflammatory Response by HT-C6, a Hydroxytyrosol Alkyl Ether Derivative. Antioxidants, 12(8), 1513. https://doi.org/10.3390/antiox12081513 https://hdl.handle.net/10630/31607 10.3390/antiox12081513 eng Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ open access application/pdf MDPI