The gene expression fingerprint of human heart failure

Tan, Fen Lai; Moravec, Christine S.; Li, Jianbo; Apperson-Hansen, Carolyn; McCarthy, Patrick M.; Young, James B.; Bond, Meredith

doi:10.1073/pnas.162370099

Cited by 242 publications

(207 citation statements)

References 31 publications

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“…[40] BNP and Ctgf were also shown to be markers for human idiopathic dilated cardiomyopathies. [41], [42] Other studies in humans show up-regulation of many other extracellular matrix related genes. [43], [44] We found that Nox4 and Lox mRNA's were increased in left ventricular tissue from 9-10 month old mdx mice, whereas oxidases Nox1 and Nox2 (Cybb) were not up-regulated ( Figure 3).…”

Section: Discussionmentioning

confidence: 98%

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Spurney

Knoblach

Pistilli

et al. 2008

Neuromuscular Disorders

136

133

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Duchenne muscular dystrophy (DMD; dystrophin-deficiency) causes dilated cardiomyopathy in the second decade of life in affected males. We studied the dystrophin-deficient mouse heart (mdx) using high frequency echocardiography, histomorphometry, and gene expression profiling. Heart dysfunction was prominent at 9-10 months of age and showed significantly increased LV internal diameter (end systole) and decreased posterior wall thickness. This cardiomyopathy was associated with a 30% decrease in shortening fraction. Histologically, there was a 10-fold increase in connective tissue volume (fibrosis). mRNA profiling with RT-PCR validation showed activation of key profibrotic genes, including Nox4 and Lox. The Nox gene family expression differed in mdx heart and skeletal muscle, where Nox2 was specifically induced in skeletal muscle while Nox4 was specifically induced in heart. This is the first report of an altered profibrotic gene expression profile in cardiac tissue of dystrophic mice showing echocardiographic evidence of cardiomyopathy.

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Section: Discussionmentioning

confidence: 98%

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Spurney

Knoblach

Pistilli

et al. 2008

Neuromuscular Disorders

136

133

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“…Microarray technology has been utilized to identify differentially expressed genes in terminally failing vs. non-failing human hearts as well as mouse transgenic HF models [15][16][17][18][19][20][21][22]. However, little has been done to systematically compare expression profiles between various animal models and human HF of different etiologies.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

Zhong

DiSilvestre

et al. 2006

Journal of Molecular and Cellular Cardiology

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Alterations of cardiac gene expression are central to ventricular dysfunction in human heart failure (HF). The canine tachycardia pacing-induced HF model is known to reproduce the main hemodynamic, echocardiographic and electrophysiological changes observed in human HF. In this study, we use this HF model to compare gene expression profiles in the left and right ventricles (LV, RV) of normal and end-stage failing canine hearts and compare the transcription profiles to those in human and murine models of HF. In end-stage HF, the LV exhibits down regulation of genes involved in energy production, cardiac contraction, and modulation of excitation-contraction coupling as compared with normal LV. The majority of transcriptomic changes between normal and end-stage canine HF were shared by the RV and LV. Genes down regulated only in the LV included those involved in aerobic energy production pathways, regulation of actin filament length, and enzymelinked receptor protein signaling pathways. In normal canine hearts, genes encoding specific components of the contractile apparatus exhibit LV-RV asymmetric expression patterns; in failing hearts, cardiac fetal transcription factors MEF2 and MITF and the stress-responsive transcription factor ATF4 showed interventricular differences in expression. The comparison among the canine tachypacing, mouse transgenic, and human HF reveals that human disease involves down regulation of genes in a broad range of biological processes while experimentally induced HF is associated with down regulation of energy pathways, and that human ischemic HF and canine HF share a similar over representation of transcriptional pathways in the up regulated genes. This study provides insights into the molecular pathways leading to end-stage tachycardia-induced HF, and into global transcriptomic differences between the animal HF models and human HF.

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“…The molecular basis, i.e. the origins and mechanisms of many alterations found in patients suffering from HF is poorly understood, but genome-wide gene expression analysis approaches are starting to reveal important associations between gene expression signatures and the pathogenesis and outcome of the disease [2][3][4]. High expectations have been raised that expression profiles might be used as a diagnostic and/or prognostic aid in disease management, e.g.…”

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confidence: 99%

“…differences in sensitivity and in the targeted sequences. These effects, together with the biological heterogeneity of the samples used, become apparent in several published array studies on HF [2,3,13,14]. In these data sets only a limited overlap of deregulated genes can be found and the deregulation of even prominent HF markers belonging to the fetal gene program, e.g.…”

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confidence: 99%