RT Journal Article
T1 Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: Mechanisms of endothelial dysfunction in chronic kidney disease
A1 Figuer, Andrea
A1 Santos, Fátima M.
A1 Ciordia, Sergio
A1 Valera Arévalo, Gemma
A1 Martín Jouve, Beatriz
A1 Hernández-Fonseca, Juan Pablo
A1 Bodega, Guillermo
A1 Ceprián, Noemí
A1 Ramírez, Rafael
A1 Carracedo Añón, Julia María
A1 Alique, Matilde
AB AimsCardiovascular pathology is the main cause of death in chronic kidney disease (CKD) patients. CKD is associated with the accumulation of uremic toxins in the bloodstream, and indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of CKD patients. We conducted an in vitro study to assess the mechanisms underlying the IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We also studied their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo.Main methodsEVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, flow cytometry, and tetraspanin expression. Cell lysates and isolated EVs were analyzed using liquid chromatography coupled with mass spectrometry, followed by Gene Set Enrichment Analysis to identify the altered pathways.Key findingsProteomic analysis of endothelial cells revealed that IS causes an increase in proteins related to adipogenesis, inflammation, and xenobiotic metabolism and a decrease in proliferation. Extracellular matrix elements, as well as proteins associated with myogenesis, response to UV irradiation, and inflammation, were found to be downregulated in IS-treated EVs. Fatty acid metabolism was also found to be increased along with adipogenesis and inflammation observed in cells.SignificanceThe treatment of endothelial cells with IS increased the expression of proteins related to adipogenesis, inflammation, and xenobiotic metabolism and was less associated with proliferation. Furthermore, EVs from cells treated with IS may mediate endothelial dysfunction, since they present fewer extracellular matrix elements, myogenesis, inflammatory factors, and proteins downregulated in response to UV radiation.
PB Elsevier
SN 0024-3205
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/117794
UL https://hdl.handle.net/20.500.14352/117794
LA eng
NO Figuer, A., Santos, F. M., Ciordia, S., Valera, G., Martín-Jouve, B., Hernández-Fonseca, J. P., Bodega, G., Ceprián, N., Ramírez, R., Carracedo, J., & Alique, M. (2024). Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: Mechanisms of endothelial dysfunction in chronic kidney disease. Life Sciences, 351, 122810. https://doi.org/10.1016/j.lfs.2024.122810
NO This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and cofounded by Fondo Europeo de Desarrollo Regional (FEDER): “PI19/00240”, “PI20/01321”, and “PI23/01109”. A.F. enjoyed the PFIS contract “FI20/00018” and F.M.S. a Sara Borrel “CD23/00049.” Also, G.V. received a contract from the Instituto de Investigación Sanitario del Hospital Universitario 12 de Octubre (i + 12) “I + 12-AY2OO414-1”. In addition, grants from Universidad de Alcalá (“Ayuda de la Línea de Actuación Excelencia para el Profesorado Universitario de la UAH”; EPU-INV-UAH/2022/001), RICORS2040; RD21/0005/0002 funded by European Union—NextGenerationEU and Comunidad de Madrid (CAM; P2022/BMD-7223 CIFRA_COR-CM), supported this work.
NO Instituto de Salud Carlos III
NO European Commission
NO Hospital Universitario 12 de Octubre
NO Universidad de Alcalá de Henares
NO Comunidad de Madrid
DS Docta Complutense
RD 6 abr 2025