Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction.
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.
Kreymborg
Karsten grosse
Kg
University of Giessen Lung Center (UGLC), Justus-Liebig-University Giessen, Germany.
Uchida
Shizuka
S
Gellert
Pascal
P
Schneider
André
A
Boettger
Thomas
T
Voswinckel
Robert
R
Wietelmann
Astrid
A
Szibor
Marten
M
Weissmann
Norbert
N
Ghofrani
Ardeschir Hossein
AH
Schermuly
Ralph
R
Schranz
Dietmar
D
Seeger
Werner
W
Braun
Thomas
T
D000818:Animals; D016000:Cluster Analysis; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D014694:Ventricular Outflow Obstruction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*