RT Journal Article
T1 Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction
A1 Carmona, Andres
A1 Guerrero, Fatima
A1 Buendia, Paula
A1 Obrero, Teresa
A1 Aljama, Pedro
A1 Carracedo, Julia
K1 Indoxyl sulfate
K1 Endothelial microvesicles
K1 Endothelial progenitor cells
K1 Endothelial dysfunction
K1 MiRNAs
K1 Chronic kidney-disease
K1 Proximal tubular cells
K1 Chronic-renal-failure
K1 Oxidative stress
K1 Circulating microparticles
K1 Extracellular vesicles
K1 Vascular repair
K1 Uremic toxins
K1 Expression
K1 Proliferation
AB Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. Indoxyl sulfate (IS) is a typical protein-bound uremic toxin that cannot be effectively cleared by conventional dialysis. Increased IS is associated with the progression of chronic kidney disease and development of cardiovascular disease. After endothelial activation by IS, cells release endothelial microvesicles (EMV) that can induce endothelial dysfunction. We developed an in vitro model of endothelial damage mediated by IS to evaluate the functional effect of EMV on the endothelial repair process developed by endothelial progenitor cells (EPCs). EMV derived from IS-treated endothelial cells were isolated by ultracentrifugation and characterized for miRNAs content. The effects of EMV on healthy EPCs in culture were studied. We observed that IS activates endothelial cells and the generated microvesicles (IsEMV) can modulate the classic endothelial roles of progenitor cells as colony forming units and form new vessels in vitro. Moreover, 23 miRNAs were contained in IsEMV including four (miR-181a-5p, miR-4454, miR-150-5p, and hsa-let-7i-5p) that were upregulated in IsEMV compared with control endothelial microvesicles. Other authors have found that miR-181a-5p, miR-4454, and miR-150-5p are involved in promoting inflammation, apoptosis, and cellular senescence. Interestingly, we observed an increase in NF kappa B and p53, and a decrease in I kappa B alpha in EPCs treated with IsEMV. Our data suggest that IS is capable of inducing endothelial vesiculation with different membrane characteristics, miRNAs and other molecules, which makes maintaining of vascular homeostasis of EPCs not fully functional. These specific characteristics of EMV could be used as novel biomarkers for diagnosis and prognosis of vascular disease.
PB Frontiers Research Foundation
SN 1664-042X
YR 2017
FD 2017-08-22
LK http://hdl.handle.net/10668/19241
UL http://hdl.handle.net/10668/19241
LA en
NO Carmona A, Guerrero F, Buendia P, Obrero T, Aljama P, Carracedo J. Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction. Front Physiol. 2017 Sep 8;8:666
DS RISalud
RD Apr 5, 2025