Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure

TY - JOUR

T1 - Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure

AU - Dickinson, Brent A

AU - Semus, Hillary M

AU - Montgomery, Rusty L

AU - Stack, Christianna

AU - Latimer, Paul A

AU - Lewton, Steven M

AU - Lynch, Joshua M

AU - Hullinger, Thomas G

AU - Seto, Anita G

AU - van Rooij, Eva

PY - 2013/6

Y1 - 2013/6

N2 - AIMS: Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease.METHODS AND RESULTS: In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression.CONCLUSIONS: Circulating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.

AB - AIMS: Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease.METHODS AND RESULTS: In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression.CONCLUSIONS: Circulating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.

KW - Angiotensin-Converting Enzyme Inhibitors

KW - Animals

KW - Biological Markers

KW - Captopril

KW - Disease Models, Animal

KW - Disease Progression

KW - Enzyme-Linked Immunosorbent Assay

KW - Gene Expression Profiling

KW - Heart Failure

KW - Hypertension

KW - Male

KW - MicroRNAs

KW - Natriuretic Peptide, Brain

KW - Oligonucleotide Array Sequence Analysis

KW - Rats

KW - Rats, Inbred Dahl

KW - Rats, Sprague-Dawley

KW - Real-Time Polymerase Chain Reaction

KW - Sodium Chloride

KW - Treatment Outcome

U2 - 10.1093/eurjhf/hft018

DO - 10.1093/eurjhf/hft018

M3 - Article

C2 - 23388090

SN - 1388-9842

VL - 15

SP - 650

EP - 659

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 6

ER -