Microarray analysis of microRNA profiles for assessing the therapeutic effects of sodium thiosulfate on end-stage renal disease combined with coronary artery calcification.

Abstract

Background: Coronary artery calcification (CAC) is a common complication in patients with end-stage renal disease (ESRD), which causes of increased cardiovascular mortality in maintenance hemodialysis patients. This study examined how sodium thiosulfate (STS) treatment affects the microRNA (miRNA) expression profiles of ESRD patients combined with CAC.

Materials and methods: A total of 18 patients with ESRD complicated with CAC were assigned to a control group that received conservative treatment or a test group that received STS treatment. The 2 groups were then sub-divided into a CGBT group (control group before treatment), TGBT group (test group before treatment), CGAT group (control group after treatment), and TGAT group (test group after treatment). Samples of peripheral venous blood were collected for analysis of biochemical indexes (hs-CRP, ALB, CHO, TG, Ca, P, BUN, Cr, bALP, iPTH, and FGF23) and used to screen for differentially expressed miRNAs that were displayed by hierarchical clustering and in a volcano plot. The functional roles of miRNA target genes were analyzed by Gene Ontology and Kyoto Encycolopedia of Genes and Genomes pathway analyses. Several miRNAs in serum samples were identified using quantitative real time PCR.

Results: STS treatment did not significantly change the biochemical indexes. A microarray analysis identified 67 miRNAs that were differentially expressed in the TGAT group vs. the TGBT group, and 28 -miRNAs that were differentially expressed in the CGAT group vs. the CGBT group. The miRNA target genes were associated with signal transduction, transcriptional regulation, cytoplasm and protein binding processes, the MAPK signaling pathway, PI3K-Akt signaling pathway, and various pathways in cancer. Validation experiments confirmed the suppressive effect of STS treatment on miR-337-5p/miR-409-5p expression and the promotive effect of STS on miR-376a-3p expression.

Conclusion: MiR-337-5p/miR-409-5p/miR-376a-3p might be key regulators involved with the therapeutic effects of STS treatment in ESRD patients associated with arterial calcification.