Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification
Journal
Arteriosclerosis, Thrombosis, and Vascular Biology
Journal Volume
37
Journal Issue
7
Pages
1402-1414
Date Issued
2017
Author(s)
Liu Y.-P.
Yeh H.-Y.
Chen H.-Y.
Lee P.-J.
Chen W.-J.
Lee Y.-M.
Abstract
Objective - Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand. Approach and Results - We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71; P=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14; P<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13; P=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135). Conclusions - The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression. ? 2017 American Heart Association, Inc.
SDGs
Other Subjects
calcifediol; fibroblast growth factor 23; microRNA; microRNA 125b; microRNA 138; osteocalcin; osteoprotegerin; transcription factor RUNX2; unclassified drug; genetic marker; microRNA; MIRN125 microRNA, human; MIRN125 microRNA, rat; age; aged; aortic tissue; apoptosis; Article; biomineralization; blood vessel calcification; disease course; disease severity; end stage renal disease; female; follow up; gene expression; human; hyperphosphatemia; in vitro study; in vivo study; major clinical study; male; phenotype; polymerase chain reaction; priority journal; risk assessment; screening; uremia; vascular smooth muscle cell; animal; Aortic Diseases; blood; cell culture; chi square distribution; complication; disease course; disease model; down regulation; genetic marker; genetic transfection; genetics; hyperphosphatemia; Kaplan Meier method; Kidney Failure, Chronic; metabolism; middle aged; multivariate analysis; odds ratio; pathology; predictive value; risk factor; severity of illness index; smooth muscle cell; Sprague Dawley rat; statistical model; thoracic aorta; time factor; uremia; Vascular Calcification; vascular smooth muscle; very elderly; Aged; Aged, 80 and over; Animals; Aorta, Thoracic; Aortic Diseases; Apoptosis; Cells, Cultured; Chi-Square Distribution; Disease Models, Animal; Disease Progression; Down-Regulation; Female; Genetic Markers; Humans; Hyperphosphatemia; Kaplan-Meier Estimate; Kidney Failure, Chronic; Logistic Models; Male; MicroRNAs; Middle Aged; Multivariate Analysis; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Odds Ratio; Predictive Value of Tests; Rats, Sprague-Dawley; Risk Factors; Severity of Illness Index; Time Factors; Transfection; Uremia; Vascular Calcification
Publisher
Lippincott Williams and Wilkins
Type
journal article