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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\u00a0=\u00a020) and patients with end\u2010stage renal disease on haemodialysis (n\u00a0=\u00a020). 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\u2010dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up\u2010regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule\u20101, surface Toll\u2010like receptor\u20104, von Willebrand Factor and reactive oxygen species. Moreover, DF down\u2010regulated HDACs expression through the PI3\/AKT signalling pathway. HDACs appear as key modulators of the CKD\u2010induced 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\u2010regulation likely\n                    <jats:bold>\u00a0<\/jats:bold>\n                    through PI3K\/AKT.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.14865","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T02:37:44Z","timestamp":1574995064000},"page":"1713-1723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Up\u2010regulation of HDACs, a harbinger of uraemic endothelial dysfunction, is prevented by defibrotide"],"prefix":"10.1111","volume":"24","author":[{"given":"Marta","family":"Palomo","sequence":"first","affiliation":[{"name":"Hematopathology Centre Diagn\u00f2stic Biom\u00e8dic (CDB) Hospital Clinic Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona (UB) Barcelona Spain"},{"name":"Josep Carreras Leukaemia Research Institute Hospital 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