Online Hemodiafiltration Inhibits Inflammation-Related Endothelial Dysfunction and Vascular Calcification of Uremic Patients Modulating miR-223 Expression in Plasma Extracellular Vesicles

• Published in: The Journal of immunology (1950) Vol. 202; no. 8; pp. 2372 - 2383
• Main Authors: Cavallari, Claudia, Dellepiane, Sergio, Fonsato, Valentina, Medica, Davide, Marengo, Marita, Migliori, Massimiliano, Quercia, Alessandro D, Pitino, Adriana, Formica, Marco, Panichi, Vincenzo, Maffei, Stefano, Biancone, Luigi, Gatti, Emanuele, Tetta, Ciro, Camussi, Giovanni, Cantaluppi, Vincenzo
• Format: Journal Article
• Language: English
• Published: United States 15.04.2019
• Subjects: Adult; Aged; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Extracellular Vesicles - immunology; Extracellular Vesicles - metabolism; Female; Gene Expression Regulation - immunology; Hemodiafiltration; Human Umbilical Vein Endothelial Cells; Humans; Inflammation - blood; Inflammation - immunology; Inflammation - pathology; Inflammation - therapy; Male; MicroRNAs - blood; MicroRNAs - immunology; Middle Aged; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - immunology; Renal Insufficiency, Chronic - pathology; Renal Insufficiency, Chronic - therapy; Uremia - blood; Uremia - immunology; Uremia - pathology; Uremia - therapy; Vascular Calcification - blood; Vascular Calcification - immunology; Vascular Calcification - pathology; Vascular Calcification - therapy
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1800747

Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized 1:1 to continue BHD or switch to mOL-HDF. Concentration, size, and microRNA content of plasma EV were evaluated for 9 mo; we then studied EV effects on inflammation, angiogenesis, and apoptosis of endothelial cells (HUVEC) and on osteoblast mineralization of vascular smooth muscle cells (VSMC). mOL-HDF treatment reduced different inflammatory markers, including circulating CRP, IL-6, and NGAL. All hemodialysis patients showed higher plasma levels of endothelial-derived EV than healthy subjects, with no significant differences between BHD and mOL-HDF. However, BHD-derived EV had an increased expression of the proatherogenic miR-223 with respect to healthy subjects or mOL-HDF. Compared with EV from healthy subjects, those from hemodialysis patients reduced angiogenesis and increased HUVEC apoptosis and VSMC calcification; however, all these detrimental effects were reduced with mOL-HDF with respect to BHD. Cell transfection with miR-223 mimic or antagomiR proved the role of this microRNA in EV-induced HUVEC and VSMC dysfunction. The switch from BHD to mOL-HDF significantly reduced systemic inflammation and miR-223 expression in plasma EV, thus improving HUVEC angiogenesis and reducing VSMC calcification.