Document Detail


Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction.
MedLine Citation:
PMID:  20673770     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible model of RVH in mice using pulmonary artery clipping (PAC), which avoids detrimental RV pressure overload and thus allows long-term survival of operated mice. Magnetic resonance imaging revealed pathognomonic changes with striking similarities to human congenital heart disease- or pulmonary arterial hypertension-patients. Comparative, microarray based transcriptome analysis of right- and left-ventricular remodeling identified distinct transcriptional responses to pressure-induced hypertrophy of either ventricle, which were mainly characterized by stronger transcriptional responses of the RV compared to the LV myocardium. Hierarchic cluster analysis revealed a RV- and LV-specific pattern of gene activity after induction of hypertrophy, however, we did not find evidence for qualitatively distinct regulatory pathways in RV compared to LV. Data mining of nearly three thousand RV-enriched genes under PAC disclosed novel potential (co)-regulators of long-term RV remodeling and hypertrophy. We reason that specific inhibitory mechanisms in RV restrict excessive myocardial hypertrophy and thereby contribute to its vulnerability to pressure overload.
Authors:
Karsten grosse Kreymborg; Shizuka Uchida; Pascal Gellert; André Schneider; Thomas Boettger; Robert Voswinckel; Astrid Wietelmann; Marten Szibor; Norbert Weissmann; Ardeschir Hossein Ghofrani; Ralph Schermuly; Dietmar Schranz; Werner Seeger; Thomas Braun
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-27
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  49     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-12-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  598-605     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
University of Giessen Lung Center (UGLC), Justus-Liebig-University Giessen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cluster Analysis
Hypertrophy, Right Ventricular / metabolism,  pathology,  physiopathology
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Ventricular Outflow Obstruction / metabolism*,  pathology,  physiopathology*

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