Document Detail


Recovery from decompensated heart failure is associated with a distinct, phase-dependent gene expression profile.
MedLine Citation:
PMID:  22480839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Clinical and experimental studies have traditionally focused on understanding the mechanisms for why a heart fails. We hypothesize that the pathways involved with myocardial recovery are not simply the reverse of those that cause heart failure. However, determining when and how a decompensated heart can recover remains unknown.
METHODS: Male C57BL/6 mice underwent minimally invasive aortic banding for 3, 4, or 6 wk with or without subsequent band removal for 1 wk (debanding). Physiologic and genomic characterization was performed with intracardiac pressure-volume recordings, rt-PCR, and microarray analysis.
RESULTS: Heart weight/body weight ratios and PV loops demonstrated a transition from compensated left ventricular hypertrophy to decompensated heart failure between 3 and 4 wk. Pressure-relief afforded by debanding allowed functional recovery and normalization of LVH after both 3 and 4, but not 6 wk of banding. Whole genome microarrays demonstrated 397 genes differentially expressed in recovered hearts, 250 genes differentially expressed in the nonrecoverable (6 wk) hearts, and only 10 genes shared by both processes. In particular, altered expression patterns of apoptotic and metalloproteinase genes correlated with the heart's ability to functionally recover.
CONCLUSIONS: This clinically-relevant model (1) allows us to temporally and mechanistically characterize the failing heart, (2) demonstrates a unique genomic signature that may predict when a failing heart can recover following pressure relief, and (3) will prove useful as a template for testing therapeutic strategies aimed at recovery of the failing heart.
Authors:
Nancy M Andersen; William E Stansfield; Ru-hang Tang; Mauricio Rojas; Cam Patterson; Craig H Selzman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-10
Journal Detail:
Title:  The Journal of surgical research     Volume:  178     ISSN:  1095-8673     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-23     Completed Date:  2013-01-10     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  72-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiomegaly / genetics*,  physiopathology*
Disease Models, Animal
Disease Progression
Genomics
Heart Failure / genetics*,  physiopathology*
Male
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Recovery of Function / physiology
Transcriptome / physiology*
Ventricular Pressure / physiology
Grant Support
ID/Acronym/Agency:
R01 HL089592/HL/NHLBI NIH HHS; R01 HL089592-02/HL/NHLBI NIH HHS; R01HL089592/HL/NHLBI NIH HHS; R01HL65619/HL/NHLBI NIH HHS; R37 HL065619/HL/NHLBI NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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