Carmona, AndresGuerrero, FatimaJimenez, Maria JoseAriza, FranciscoAgüera, Marisa LObrero, TeresaNoci, VictoriaMuñoz-Castañeda, Juan RafaelRodríguez, MarianoSoriano, SagrarioMoreno, Juan AntonioMartin-Malo, AlejandroAljama, Pedro2023-02-092023-02-092020-07-16Carmona A, Guerrero F, Jimenez MJ, Ariza F, Agüera ML, Obrero T, et al. Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease. Front Cell Dev Biol. 2020 Aug 6;8:7392296-634Xhttp://hdl.handle.net/10668/16160Patients 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Chronic kidney diseaseMicroRNAsMicrovesiclesMonocytes CD14+CD16++Vascular smooth muscle cellsMicroRNAsMuscle, smooth, vascularAnnexin A5Uremic toxinsAging, prematureMonocytesKidney transplantationDown-regulationGlomerular filtration rateresearch article32850849open accessAnexina A5Envejecimiento prematuroMicroARNsMonocitosMúsculo liso vascularTasa de filtración glomerularTrasplante de riñónTóxinas urémicas10.3389/fcell.2020.00739PMC7423998https://www.frontiersin.org/articles/10.3389/fcell.2020.00739/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423998/pdf