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

Brent A Dickinson, Hillary M Semus, Rusty L Montgomery, Christianna Stack, Paul A Latimer, Steven M Lewton, Joshua M Lynch, Thomas G Hullinger, Anita G Seto, Eva van Rooij

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)650-9
Number of pages10
JournalEuropean Journal of Heart Failure
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Angiotensin-Converting Enzyme Inhibitors
  • Animals
  • Biological Markers
  • Captopril
  • Disease Models, Animal
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling
  • Heart Failure
  • Hypertension
  • Male
  • MicroRNAs
  • Natriuretic Peptide, Brain
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Rats, Inbred Dahl
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Sodium Chloride
  • Treatment Outcome

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