Circulating long noncoding RNA DKFZP434I0714 predicts adverse cardiovascular outcomes in patients with end-stage renal disease
Journal
International Journal of Cardiology
Journal Volume
277
Pages
212-219
Date Issued
2019
Author(s)
Abstract
Background: Cardiovascular (CV) diseases are major causes of mortality in uremic patients. Conventional risk factors fail to identify uremic patients with increased propensity for adverse CV outcomes. We aimed to test the hypothesis that circulating long noncoding RNAs (lncRNAs) could be a prognostic marker to predict adverse CV outcomes in uremic patients. Methods and results: Plasma lncRNAs were profiled in patients with end-stage renal disease (ESRD, n = 28) or chronic kidney disease (CKD, n = 8) and in healthy (n = 12) subjects by RNA sequencing. A total of 179 lncRNAs were significantly dysregulated with ESRD; the expression signature of plasma lncRNAs distinguished ESRD from both CKD and control samples. Analysis on a microarray dataset obtained from renal biopsy samples of patients with advanced kidney disease (GSE66494) revealed that a significant proportion of plasma lncRNAs (30.7%) and mRNAs (49.5%) dysregulated with uremia were similarly dysregulated in diseased kidneys, suggesting that plasma RNA profiles mirror the transcriptomal changes in diseased kidney tissues. Further analyses identified eight plasma lncRNAs as potential predictors of adverse CV outcomes in uremic patients. Validation study in an independent cohort of ESRD patients (n = 111) confirmed that elevated plasma lncRNA DKFZP434I0714 is a significant independent predictor of adverse CV outcomes in uremic patients. Additional experiments demonstrated the functional involvement of DKFZP434I0714 in the pathogenesis of endothelial dysfunction. Conclusions: In summary, plasma lncRNA expression signature reflects the disease states of uremia. Elevated plasma levels of lncRNA DKFZP434I0714 in uremic patients portend a worse CV outcome and warrant closer monitoring and more aggressive management. ? 2018 Elsevier B.V.
SDGs
Other Subjects
endothelial nitric oxide synthase; intercellular adhesion molecule 1; kruppel like factor 2; long untranslated RNA; messenger RNA; vascular cell adhesion molecule 1; long untranslated RNA; aortic endothelial cell; apoptosis; Article; blood level; cardiovascular disease; cell adhesion; chronic kidney failure; clinical article; cohort analysis; controlled study; down regulation; end stage renal disease; gene control; gene expression; gene knockdown; gene overexpression; human; human aortic endothelial cell; human cell; hypoxia; kidney biopsy; kidney disease; microarray analysis; priority journal; prognosis; protein expression level; RNA sequence; upregulation; uremia; validation study; blood; cardiovascular disease; chronic kidney failure; genetics; predictive value; treatment outcome; Cardiovascular Diseases; Humans; Kidney Failure, Chronic; Predictive Value of Tests; RNA, Long Noncoding; Treatment Outcome
Publisher
Elsevier Ireland Ltd
Type
journal article