Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis
Autor: | Thomas Quertermous, Mingming Zhao, Daniel Bernstein, Roger A. Wagner, Sara Farahani, Takashi Urashima, Giovanni Fajardo |
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Rok vydání: | 2008 |
Předmět: |
Male
medicine.medical_specialty Pathology Heart disease Physiology Gene Expression Muscle hypertrophy Mice Afterload Physiology (medical) medicine.artery Internal medicine Laser-Doppler Flowmetry medicine Animals Edema Ventricular remodeling Oligonucleotide Array Sequence Analysis Heart Failure Ventricular Remodeling business.industry Organ Size medicine.disease Survival Analysis Pulmonary Valve Stenosis Echocardiography Heart failure Pulmonary valve stenosis Circulatory system Pulmonary artery Tetralogy of Fallot Ventricular Function Right Innovative Methodology Cardiology Cardiology and Cardiovascular Medicine business |
Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 295:H1351-H1368 |
ISSN: | 1522-1539 0363-6135 |
DOI: | 10.1152/ajpheart.91526.2007 |
Popis: | Right ventricular (RV) dysfunction is a common long-term complication in patients after the repair of congenital heart disease. Previous investigators have examined the cellular and molecular mechanisms of left ventricular (LV) remodeling, but little is known about the stressed RV. Our purpose was to provide a detailed physiological characterization of a model of RV hypertrophy and failure, including RV-LV interaction, and to compare gene alterations between afterloaded RV versus LV. Pulmonary artery constriction was performed in 86 mice. Mice with mild and moderate pulmonary stenosis (PS) developed stable hypertrophy without decompensation. Mice with severe PS developed edema, decreased RV function, and high mortality. Tissue Doppler imaging demonstrated septal dyssynchrony and deleterious RV-LV interaction in the severe PS group. Microarray analysis showed 196 genes with increased expression and 1,114 with decreased expression. Several transcripts were differentially increased in the afterloaded RV but not in the afterloaded LV, including clusterin, neuroblastoma suppression of tumorigenicity 1, Dkk3, Sfrp2, formin binding protein, annexin A7, and lysyl oxidase. We have characterized a murine model of RV hypertrophy and failure, providing a platform for studying the physiological and molecular events of RV remodeling. Although the molecular responses of the RV and LV to afterload stress are mostly concordant, there are several key differences, which may represent targets for RV failure-specific therapy. |
Databáze: | OpenAIRE |
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