RT Journal Article
T1 Passage Number-Induced Replicative Senescence Modulates the Endothelial Cell Response to Protein-Bound Uremic Toxins
A1 Guerrero, Fatima
A1 Carmona, Andres
A1 Jimenez, Maria Jose
A1 Obrero, Teresa
A1 Pulido, Victoria
A1 Moreno, Juan Antonio
A1 Soriano, Sagrario
A1 Martin-Malo, Alejandro
A1 Aljama, Pedro
K1 aging
K1 indoxyl sulfate
K1 p-cresol
K1 endothelial cells
K1 endothelial dysfunction
K1 senescence
K1 Smooth-muscle-cells
K1 Indoxyl sulfate
K1 P-cresol
K1 Stress
K1 Proliferation
K1 Disease
AB Endothelial 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.
PB Mdpi
YR 2021
FD 2021-10-01
LK https://hdl.handle.net/10668/25865
UL https://hdl.handle.net/10668/25865
LA en
DS RISalud
RD Apr 10, 2025