Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats
Open Access
- 5 January 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (1), e15859
- https://doi.org/10.1371/journal.pone.0015859
Abstract
The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure.Keywords
This publication has 47 references indexed in Scilit:
- Controversies in ventricular remodellingThe Lancet, 2006
- Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failurePhysiological Genomics, 2005
- The right ventricle in pulmonary hypertensionCoronary Artery Disease, 2005
- Treatment of Pulmonary Arterial HypertensionNew England Journal of Medicine, 2004
- Dynamic changes of gene expression in hypoxia-induced right ventricular hypertrophyAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- The prostaglandins epoprostenol and iloprost increase left ventricular contractility in vivoIntensive Care Medicine, 2003
- Cardiac Hypertrophy: The Good, the Bad, and the UglyAnnual Review of Physiology, 2003
- Stage-dependent activation of cell cycle and apoptosis mechanisms in the right ventricle by pressure overloadBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2002
- Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failureThe American Journal of Cardiology, 1998
- Role of Endogenous Endothelin in Chronic Heart FailureCirculation, 1997