LAUSR

Objectives: Hypertension (HTN) and chronic kidney disease (CKD) are global health disorders that are epidemiologically associated. Vascular injury is an early manifestation in HTN and contributes to CKD. It is characterized by vascular dysfunction and remodeling and gene expression changes. MicroRNAs (miRs) are important non-coding RNA gene expression regulators, but their implication in vascular injury remains unclear. We aimed to identify differentially expressed (DE) miRs in small arteries of HTN and CKD human subjects to get insight into pathophysiological molecular mechanisms in these conditions. Methods: Normotensive, HTN (systolic blood pressure (BP) >135 mmHg or diastolic BP of 85–115 mmHg with BpTRU) and CKD subjects (estimated glomerular filtration rate < 60 mL/min/m2) (n = 15–16) were studied. Small arteries were isolated from subcutaneous gluteal biopsies and RNA extracted for small and total RNA sequencing using Illumina HiSeq-2500. EdgeR was used for differential expression analysis, TargetScan to predict DE miR targets in the DE mRNAs and reverse transcription-quantitative PCR (RT-qPCR) to confirm RNA differential expression and find vascular cells expressing these RNAs. Results: DE miRs were identified (P < 0.05) uniquely associated with HTN (3↑ and 6↓) and CKD (42↑ and 39↓) and in both groups (2↑). Correlation between RNA-sequencing and RT-qPCR data was demonstrated for 3 miRs (of 14 tested) including the down-regulated miR-338–3p uniquely associated with CKD (r = 0.91, P < 10–16). ACER2, CCL14 and GPX3 were predicted targets for this miR. miR-338–3p and its predicted targets were found to be expressed in endothelial cells. Conclusion: miR-338–3p down-regulation was found in small arteries uniquely associated with CKD.