Guerrero, FatimaCarmona, AndresJimenez, Maria JoseObrero, TeresaPulido, VictoriaMoreno, Juan AntonioSoriano, SagrarioMartín-Malo, AlejandroAljama, Pedro2022-07-192022-07-192021-10-19Guerrero F, Carmona A, Jimenez MJ, Obrero T, Pulido V, Moreno JA, et al. Passage Number-Induced Replicative Senescence Modulates the Endothelial Cell Response to Protein-Bound Uremic Toxins. Toxins. 2021 Oct 19;13(10):738http://hdl.handle.net/10668/3806Endothelial aging may be induced early in pathological situations. The uremic toxins indoxyl sulfate (IS) and p-cresol (PC) accumulate in the plasma of chronic kidney disease (CKD) patients, causing accelerated endothelial aging, increased cardiovascular events and mortality. However, the mechanisms by which uremic toxins exert their deleterious effects on endothelial aging are not yet fully known. Thus, the aim of the present study is to determine the effects of IS and PC on endothelial damage and early senescence in cultured human umbilical vein endothelial cells (HUVECs). Hence, we establish an in vitro model of endothelial damage mediated by different passages of HUVECs and stimulated with different concentrations of IS and PC to evaluate functional effects on the vascular endothelium. We observe that cell passage-induced senescence is associated with apoptosis, ROS production and decreased endothelial proliferative capacity. Similarly, we observe that IS and PC cause premature aging in a dose-dependent manner, altering HUVECs' regenerative capacity, and decreasing their cell migration and potential to form vascular structures in vitro. In conclusion, IS and PC cause accelerated aging in HUVECs, thus contributing to endothelial dysfunction associated with CKD progression.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AgingIndoxyl sulfateP-cresolEndothelial cellsEndothelial dysfunctionSenescenceEnvejecimientoCélulas endotelialesSenescenciaIndicánHidroxitolueno butiladoTóxinas urémicasMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell MovementMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::CresolsMedical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Endothelium, VascularMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cells::Human Umbilical Vein Endothelial CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Indoles::IndicanMedical Subject Headings::Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, ChronicMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Oxygen Compounds::Reactive Oxygen SpeciesMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cells::Human Umbilical Vein Endothelial CellsMedical Subject Headings::Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, ChronicMedical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronicresearch article34679030open access10.3390/toxins131007382072-6651PMC8538293