Journal article
Genetic Enhancement of Ventricular Contractility Protects against Pressure-Overload-Induced Cardiac Dysfunction
Journal of molecular and cellular cardiology, Vol.37(5), pp.979-987
2004
DOI: 10.1016/j.yjmcc.2004.07.010
PMID: 15522275
Abstract
In response to pressure-overload, cardiac function deteriorates and may even progress to fulminant heart failure and death. Here we questioned if genetic enhancement of left ventricular (LV) contractility protects against pressure-overload. Transgenic (TG) mice with cardiac-restricted overexpression (66-fold) of the α
1A-adrenergic receptor (α
1A-AR) and their non-TG (NTG) littermates, were subjected to transverse aorta constriction (TAC)-induced pressure-overload for 12 weeks. TAC-induced hypertrophy was similar in the NTG and TG mice but the TG mice were less likely to die of heart failure compared to the non-TG animals (
P <0.05). The hypercontractile phenotype of the TG mice was maintained over the 12-week period following TAC with LV fractional shortening being significantly greater than in the NTG mice (42±2 vs 29±1%,
P <0.01). In the TG animals, 11-week β-AR-blockade with atenolol neither induced hypertrophy nor suppressed the hypercontractile phenotype. The hypertrophic response to pressure-overload was not altered by cardiac α
1A-AR overexpression. Moreover, the inotropic phenotype of α
1A-AR overexpression was well maintained under conditions of pressure overload. Although the functional decline in contractility with pressure overload was similar in the TG and NTG animals, given that contractility was higher before TAC in the TG mice, their LV function was better preserved and heart failure deaths were fewer after induction of pressure overload.
Details
- Title: Subtitle
- Genetic Enhancement of Ventricular Contractility Protects against Pressure-Overload-Induced Cardiac Dysfunction
- Creators
- Xiao-Jun Du - The Heart Research InstituteLin Fang - Victor Chang Cardiac Research InstituteXiao-Ming Gao - The Heart Research InstituteHelen Kiriazis - The Heart Research InstituteXinheng Feng - The Heart Research InstituteElodie Hotchkin - The Heart Research InstituteAngela M. Finch - Victor Chang Cardiac Research InstituteHervé Chaulet - Victor Chang Cardiac Research InstituteRobert M. Graham - Victor Chang Cardiac Research Institute
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.37(5), pp.979-987
- DOI
- 10.1016/j.yjmcc.2004.07.010
- PMID
- 15522275
- NLM abbreviation
- J Mol Cell Cardiol
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 2004
- Academic Unit
- Anatomy and Cell Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984284455302771
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