microRNAs are dysregulated in the cerebral microvasculature of CKD mice

Abstract

Vascular calcification arises during chronic kidney disease (CKD), and increases the risk of cardiovascular mortality. In CKD, alterations of cerebral circulation were linked with an increase in ischemic strokes and behavioral troubles. Studying pathophysiological mechanisms of calcifications and detecting new biomarkers in the cerebral circulation is thus an important issue. microRNAs are small non-coding, single-stranded RNAs that regulate messenger RNAs at the post-transcriptional level. They are involved in numerous pathologies and represent new opportunities to develop disease predictors. We used RT-qPCR to quantify endothelial-specific microRNAs in cerebral arterioles from WT mice and from pathological models of CKD. We used four mice groups: WT SHAM, WT CKD, Apolipoprotein E Knock-Out (ApoE-KO) SHAM, ApoE-KO CKD. Brains were removed after two and ten weeks of uremia and RNA from cerebral arterioles was extracted. miR-17 and miR-126 were the most dysregulated in the pathological conditions, at both the second week and tenth week of uremia. Our results suggest that miR-17 and miR-126 are potential new biomarkers of cerebral troubles of CKD patients and new therapeutic targets for innovative treatments.

Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients

“…Dysregulation of miRNAs has been linked to the pathophysiology of many diseases, including kidney and cardiovascular diseases 5–7 . Our team reported that miR-126 and -223 levels were altered in the aortic wall and serum in murine models of CKD 8 , and in the microcirculation of the brain of CKD mice 9 . Human targets of these miRNAs are shown in Supplementary Table 1.…”

Co-Expression Analysis of Blood Cell Genome Expression to Preliminary Investigation of Regulatory Mechanisms in Uremia

“…The role of miRNAs in chronic kidney disease (CKD) has recently gained increased attention [38,39]. In this study, we found 15 key miRNAs that were significantly enriched in three co-expressed modules.…”

miR-223 and other miRNA's evaluation in chronic kidney disease: Innovative biomarkers and therapeutic tools

“…There is a direct correlation between the accumulation of uremic toxins and their biological and toxic effect in patients [15]. To assess this, we tested the effect of one of the most well-known uremic toxin inorganic phosphate in an in vitro model of vascular calcification: it consisted of human primary cultures of vascular smooth muscle cells (VSMCs) that acquired a pro-calcifying phenotype in presence of pathological levels of inorganic phosphate (Pi) [[16], [17], [18], [19]]. In this model, we found that Pi increased markedly the level of miR-223 [17].…”

“…Deregulation of cerebral blood flow and protection of the brain have been reported in CKD and are responsible for ischemic strokes and behavioral troubles. We quantified the expression of miR-17 and miR-126 in endothelial cells in cerebral arterioles of WT mice and of pathological models of CKD using RT-qPCR and showed that miR-17 and miR-126 are deregulated and can be used as new biological markers of cerebral troubles of patients in CKD [19].…”