RT Journal Article T1 Role of endothelial microvesicles released by p-cresol on endothelial dysfunction A1 Guerrero, Fatima A1 Carmona, Andres A1 Obrero, Teresa A1 Jiménez, Maria Jose A1 Soriano, Sagrario A1 Moreno, Juan Antonio A1 Martín-Malo, Alejandro A1 Aljama, Pedro K1 Endothelial cells K1 Human umbilical vein endothelial cells K1 Uremic toxins K1 Cresols K1 P-cresol K1 Células endoteliales K1 Células endoteliales de la vena umbilical humana K1 Tóxinas urémicas K1 Cresoles AB Protein bound uremic toxins, such as p-cresol, cannot be effectively removed by conventional dialysis techniques and are accumulated in plasma, thus contributing to progression of both chronic kidney disease (CKD) and cardiovascular disease (CVD). Pathological effects of uremic toxins include activation of inflammatory response, endothelial dysfunction and release of endothelial microvesicles. To date, the role of p-cresol in endothelial microvesicles formation has not been analyzed. The aim of the present study was evaluate the effects of endothelial microvesicles released by p-cresol (PcEMV) on endothelial dysfunction. An in vitro model of endothelial damage mediated by p-cresol was proposed to evaluate the functional effect of PcEMV on the endothelial repair process carried out by endothelial cells and microRNA (miRNA) that could be involved in this process. We observed that p-cresol induced a greater release of microvesicles in endothelial cells. These microvesicles altered regenerative capacity of endothelial cells, decreasing their capacity for cell migration and their potential to form vascular structures in vitro. Moreover, we observed increased cellular senescence and a deregulation of miRNA-146b-5p and miRNA-223-3p expression in endothelial cells treated with endothelial microvesicles released by p-cresol. In summary our data show that microvesicles generated in endothelial cells treated with p-cresol (PcEMV) interfere with the endothelial repair process by decreasing the migratory capacity, the ability to form new vessels and increasing the senescence of mature endothelial cells. These alterations could be mediated by the upregulation of miRNA-146b-5p and miRNA-223-3p. PB Springer Nature YR 2020 FD 2020-06-30 LK http://hdl.handle.net/10668/4340 UL http://hdl.handle.net/10668/4340 LA en NO Guerrero F, Carmona A, Obrero T, Jiménez MJ, Soriano S, Moreno JA, et al. Role of endothelial microvesicles released by p-cresol on endothelial dysfunction. Sci Rep. 2020 Jun 30;10(1):10657 DS RISalud RD Apr 6, 2025