Abstract
Objective: Non-coding RNA (ncRNA)-mediated targeting of various genes regulates the molecular mechanisms of the pathogenesis of hypertension (HTN). However, very few circulating long ncRNAs (lncRNAs) have been reported to be altered in essential HTN. The aim of this study was to identify simultaneously the lncRNA profiles in circulating plasma and packaged them into exosomes associated with UAE in HTN using deep sequencing technology. We also assessed the effect of the biofluid origin on lncRNA signature and regulated pathways. Design and method: In a cohort of hypertensive patients with (n = 22) or without urinary albumin excretion (UAE) (n = 26), we analyzed by next generation sequencing the lncRNA profile associated to UAE. Then, long Non-Coding RNA target predictions and molecular pathways analyses were performed through GO terms and KEGG pathways. Results: Plasma exosomes showed higher diversity and fold change of lncRNAs than plasma, and low transcript overlapping was found between the two biofluids. The majority of unique differentially expressed lncRNA in the exosome fraction were downregulated (71%) in albuminuric patients and 61% in plasma samples. In addition, in plasma samples only 40% of statistically significant transcripts had a log2 fod change higher or equal to 2 or lower or equal to -2, compared with 100% top lncRNAs in exosomal fraction. Enrichment analysis identified different biological pathways regulated in plasma or exosome fraction, which were implicated in fatty acid metabolism, extracellular matrix, and mechanisms of sorting ncRNAs into exosomes, while plasma pathways were implicated in genome reorganization, interference with RNA polymerase, and as scaffolds for assembling transcriptional regulators. Conclusions: Our study found a biofluid specific lncRNA profile associated with albuminuria, with higher diversity in exosomal fraction, which identifies several potential targets that may be utilized to study mechanisms of albuminuria and cardiovascular damage.
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