Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/181834
Title: Up-regulation of HDACs, a harbinger of uremic endothelial dysfunction, is prevented by defibrotide
Author: Palomo, Marta
Vera Rivera, Manel
Martin-Rodriguez, Susana
Torramade Moix, Sergi
Martínez Sánchez, Julia
Moreno Castaño, Ana Belén
Carreras, Enric
Escolar Albaladejo, Ginés
Cases Amenós, A. (Aleix)
Diaz Ricart, M. Isabel
Keywords: Insuficiència renal crònica
Inflamació
Chronic renal failure
Inflammation
Issue Date: 28-Nov-2019
Publisher: John Wiley & Sons
Abstract: Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end-stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose-dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up-regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule-1, surface Toll-like receptor-4, von Willebrand Factor and reactive oxygen species. Moreover, DF down-regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD-induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up-regulation likely through PI3K/AKT.
Note: Reproducció del document publicat a: https://doi.org/10.1111/jcmm.14865
It is part of: Journal of Cellular and Molecular Medicine, 2019, vol. 24, num. 2, p. 1713-1723
URI: http://hdl.handle.net/2445/181834
Related resource: https://doi.org/10.1111/jcmm.14865
ISSN: 1582-1838
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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