%0 Journal Article
%A Carmona, Andres
%A Guerrero, Fatima
%A Jimenez, Maria Jose
%A Ariza, Francisco
%A Agüera, Marisa L
%A Obrero, Teresa
%A Noci, Victoria
%A Muñoz-Castañeda, Juan Rafael
%A Rodríguez, Mariano
%A Soriano, Sagrario
%A Moreno, Juan Antonio
%A Martin-Malo, Alejandro
%A Aljama, Pedro
%T Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease.
%D 2020
%@ 2296-634X
%U http://hdl.handle.net/10668/16160
%X Patients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications. Forty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)]. In all these patients, we evaluated the quantitative changes in microRNAs (miRNAs), CD14+C16++ monocytes number, and microvesicles (MV) concentration [both total MV, and monocytes derived MV (CD14+Annexin V+CD16+)]. To understand the molecular mechanism involved in senescence and osteogenic transdifferentation of vascular smooth muscle cells (VSMC), these cells were stimulated with MV isolated from THP-1 monocytes treated with uremic toxins (txMV). A miRNA array was used to investigate serum miRNAs profile in CKD patients. Reduced expression levels of miRNAs-126-3p, -191-5p and -223-3p were observed in CKD4-5 and HD patients as compared to KT. This down-regulation disappeared after KT, even when lower glomerular filtration rates (eGFR) persisted. Moreover, HD patients had higher percentage of proinflammatory monocytes (CD14+CD16++) and MV derived of proinflammatory monocytes (CD14+Annexin V+CD16+) than the other groups. In vitro studies showed increased expression of osteogenic markers (BMP2 and miRNA-223-3p), expression of cyclin D1, β-galactosidase activity and VSMC size in those cells treated with txMV. CKD patients present a specific circulating miRNAs expression profile associated with the microinflammatory state. Furthermore, microvesicles generated by monocytes treated with uremic toxins induce early senescence and osteogenic markers (BMP2 and miRNA-223-3p) in VSMC.
%K Chronic kidney disease
%K MicroRNAs
%K Microvesicles
%K Monocytes CD14+CD16++
%K Vascular smooth muscle cells
%~