Biventricular remodeling in murine models of right ventricular pressure overload.
Right ventricular (RV) failure is a major cause of mortality in acute or chronic lung disease and left heart failure. The objective of this study was to demonstrate a percutaneous approach to study biventricular hemodynamics in murine models of primary and secondary RV pressure overload (RVPO) and further explore biventricular expression of two key proteins that regulate cardiac remodeling: calcineurin and transforming growth factor beta 1 (TGFβ1).


METHODS
Adult, male mice underwent constriction of the pulmonary artery or thoracic aorta as models of primary and secondary RVPO, respectively. Conductance catheterization was performed followed by tissue analysis for changes in myocyte hypertrophy and fibrosis.


RESULTS
Both primary and secondary RVPO decreased biventricular stroke work however RV instantaneous peak pressure (dP/dtmax) and end-systolic elastance (Ees) were preserved in both groups compared to controls. In contrast, left ventricular (LV) dP/dtmax and LV-Ees were unchanged by primary, but reduced in the secondary RVPO group. The ratio of RV:LV ventriculo-arterial coupling was increased in primary and reduced in secondary RVPO. Primary and secondary RVPO increased RV mass, while LV mass decreased in primary and increased in the secondary RVPO groups. RV fibrosis and hypertrophy were increased in both groups, while LV fibrosis and hypertrophy were increased in secondary RVPO only. RV calcineurin expression was increased in both groups, while LV expression increased in secondary RVPO only. Biventricular TGFβ1 expression was increased in both groups.


CONCLUSIONS
These data identify distinct effects of primary and secondary RVPO on biventricular structure, function, and expression of key remodeling pathways.
Molecular Cardiology Research Institute, Tufts University School of Medicine, Boston, Massachusetts, USA. Nkapur@tuftsmedicalcenter.org
Navin K
NK
Kapur
Vikram
V
Paruchuri
Mark J
MJ
Aronovitz
Xiaoying
X
Qiao
Emily E
EE
Mackey
Gerard H
GH
Daly
Kishan
K
Ughreja
Jonathan
J
Levine
Robert
R
Blanton
Nicholas S
NS
Hill
Richard H
RH
Karas
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006329:Heart Conduction System; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D008297:Male; D051379:Mice; D009929:Organ Size; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D018497:Ventricular Dysfunction, Right / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
D053773:Transforming Growth Factor beta1; D019703:Calcineurin