Molecular Signature of a Right Heart Failure Program in Chronic Severe Pulmonary Hypertension
- 1 December 2011
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 45 (6), 1239-1247
- https://doi.org/10.1165/rcmb.2010-0412oc
Abstract
Right heart failure is the cause of death of most patients with severe pulmonary arterial hypertensive (PAH) disorders, yet little is known about the cellular and molecular causes of right ventricular failure (RVF). We first showed a differential gene expression pattern between normal rat right and left ventricles, and postulated the existence of a molecular right heart failure program that distinguishes RVF from adaptive right ventricular hypertrophy (RVH), and that may differ in some respects from a left heart failure program. By means of microarrays and transcriptional sequencing strategies, we used two models of adaptive RVH to characterize a gene expression pattern reflective of growth and the maintenance of myocardial structure. Moreover, two models of RVF were associated with fibrosis, capillary rarefaction, the decreased expression of genes encoding the angiogenesis factors vascular endothelial growth factor, insulin-like growth factor 1, apelin, and angiopoeitin-1, and the increased expression of genes encoding a set of glycolytic enzymes. The treatment of established RVF with a β-adrenergic receptor blocker reversed RVF, and partly reversed the molecular RVF program. We conclude that normal right and left ventricles demonstrate clearly discernable differences in the expression of mRNA and microRNA, and that RVH and RVF are characterized by distinct patterns of gene expression that relate to cell growth, angiogenesis, and energy metabolism.Keywords
This publication has 56 references indexed in Scilit:
- Effects of Right Ventricular Ejection Fraction on Outcomes in Chronic Systolic Heart FailureCirculation, 2010
- The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricleJournal of Molecular Medicine, 2009
- Experimentally observed phenomena on cardiac energetics in heart failure emerge from simulations of cardiac metabolismProceedings of the National Academy of Sciences of the United States of America, 2009
- microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heartGenes & Development, 2008
- Energy metabolism in heart failure and remodellingCardiovascular Research, 2008
- Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesisThe EMBO Journal, 2008
- Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernationProceedings of the National Academy of Sciences of the United States of America, 2008
- In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failureAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- MicroRNA-133 controls cardiac hypertrophyNature Medicine, 2007
- A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failureProceedings of the National Academy of Sciences of the United States of America, 2006