BACKGROUND: The most common cause of chronic heart failure in the US is secondary or primary dilated cardiomyopathy (DCM). The DCM phenotype exhibits changes in the expression of genes that regulate contractile function and pathologic hypertrophy. However, it is unclear if any of these alterations in gene expression are disease producing or modifying. MATERIALS AND METHODS: One approach to providing evidence for cause-effect of a disease-influencing gene is to quantitatively compare changes in phenotype to changes in gene expression by employing serial measurements in a longitudinal experimental design. We investigated the quantitative relationships between changes in gene expression and phenotype n 47 patients with idiopathic DCM. In endomyocardial biopsies at baseline and 6 months later, we measured mRNA expression of genes regulating contractile function (beta-adrenergic receptors, sarcoplasmic reticulum Ca(2) + ATPase, and alpha- and beta-myosin heavy chain isoforms) or associated with pathologic hypertrophy (beta-myosin heavy chain and atrial natriuretic peptide), plus beta-adrenergic receptor protein expression. Left ventricular phenotype was assessed by radionuclide ejection fraction. RESULTS: Improvement in DCM phenotype was directly related to a coordinate increase in alpha- and a decrease in beta-myosin heavy chain mRNA expression. In contrast, modification of phenotype was unrelated to changes in the expression of beta(1)- or beta(2)-adrenergic receptor mRNA or protein, or to the mRNA expression of sarcoplasmic reticulum Ca(2) + ATPase and atrial natriuretic peptide. CONCLUSION: We conclude that in human DCM, phenotypic modification is selectively associated with myosin heavy chain isoform changes. These data support the hypothesis that myosin heavy chain isoform changes contribute to disease progression in human DCM.
RCT Entities:
BACKGROUND: The most common cause of chronic heart failure in the US is secondary or primary dilated cardiomyopathy (DCM). The DCM phenotype exhibits changes in the expression of genes that regulate contractile function and pathologic hypertrophy. However, it is unclear if any of these alterations in gene expression are disease producing or modifying. MATERIALS AND METHODS: One approach to providing evidence for cause-effect of a disease-influencing gene is to quantitatively compare changes in phenotype to changes in gene expression by employing serial measurements in a longitudinal experimental design. We investigated the quantitative relationships between changes in gene expression and phenotype n 47 patients with idiopathic DCM. In endomyocardial biopsies at baseline and 6 months later, we measured mRNA expression of genes regulating contractile function (beta-adrenergic receptors, sarcoplasmic reticulum Ca(2) + ATPase, and alpha- and beta-myosin heavy chain isoforms) or associated with pathologic hypertrophy (beta-myosin heavy chain and atrial natriuretic peptide), plus beta-adrenergic receptor protein expression. Left ventricular phenotype was assessed by radionuclide ejection fraction. RESULTS: Improvement in DCM phenotype was directly related to a coordinate increase in alpha- and a decrease in beta-myosin heavy chain mRNA expression. In contrast, modification of phenotype was unrelated to changes in the expression of beta(1)- or beta(2)-adrenergic receptor mRNA or protein, or to the mRNA expression of sarcoplasmic reticulum Ca(2) + ATPase and atrial natriuretic peptide. CONCLUSION: We conclude that in humanDCM, phenotypic modification is selectively associated with myosin heavy chain isoform changes. These data support the hypothesis that myosin heavy chain isoform changes contribute to disease progression in humanDCM.
Authors: Brian L Stauffer; Karen Dockstader; Gloria Russell; Jamie Hijmans; Lisa Walker; Mackenzie Cecil; Kimberly Demos-Davies; Allen Medway; Timothy A McKinsey; Carmen C Sucharov Journal: Biochem Biophys Res Commun Date: 2015-04-29 Impact factor: 3.575
Authors: David P Kao; Brian D Lowes; Edward M Gilbert; Wayne Minobe; L Elaine Epperson; Leslie K Meyer; Debra A Ferguson; Ann Kirkpatrick Volkman; Ronald Zolty; C Douglas Borg; Robert A Quaife; Michael R Bristow Journal: Circ Cardiovasc Genet Date: 2015-01-30
Authors: Crystal M Reynolds; Hagir B Suliman; John W Hollingsworth; Karen E Welty-Wolf; Martha Sue Carraway; Claude A Piantadosi Journal: Free Radic Biol Med Date: 2008-11-27 Impact factor: 7.376
Authors: Katrin Wenzel; Gerd Wallukat; Fatimunnisa Qadri; Norbert Hubner; Herbert Schulz; Oliver Hummel; Florian Herse; Arnd Heuser; Robert Fischer; Harald Heidecke; Friedrich C Luft; Dominik N Muller; Rainer Dietz; Ralf Dechend Journal: PLoS One Date: 2010-02-24 Impact factor: 3.240