title: Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: miRagen Therapeutics, 6200 Lookout Rd, Boulder, CO 80301, USA.
authors: Brent A
authors: BA
authors: Dickinson
authors: Hillary M
authors: HM
authors: Semus
authors: Rusty L
authors: RL
authors: Montgomery
authors: Christianna
authors: C
authors: Stack
authors: Paul A
authors: PA
authors: Latimer
authors: Steven M
authors: SM
authors: Lewton
authors: Joshua M
authors: JM
authors: Lynch
authors: Thomas G
authors: TG
authors: Hullinger
authors: Anita G
authors: AG
authors: Seto
authors: Eva
authors: E
authors: van Rooij
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002216:Captopril / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D006973:Hypertension / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000097:blood; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012965:Sodium Chloride / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D035683:MicroRNAs; D020097:Natriuretic Peptide, Brain; D012965:Sodium Chloride; D002216:Captopril
keywords: AntimiR therapy; Biomarker; Heart failure; miR-208a; microRNA