Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays

Ellinghaus, Peter; Scheubel, R.; Dobrev, Dobromir; Ravens, Ursula; Holtz, Juergen; Huetter, Joachim; Nielsch, Ulrich; Morawietz, Henning

doi:10.1016/j.jtcvs.2004.08.031

Cited by 100 publications

(80 citation statements)

References 22 publications

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“…Previous reports have shown that atrial and ventricular gene expression patterns are varied and showed specific expression patterns in response to stress and disease (2,3,7,35). However, both our data and those of Ruel et al (30) indicated a role for altered transcription and suggested possible modes for enhanced cardioprotection.…”

Section: Resultscontrasting

confidence: 44%

Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart

McCully

Bhasin

Daly

et al. 2009

Physiological Genomics

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scriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart. Physiol Genomics 38: 125-137, 2009. First published May 19, 2009 doi:10.1152/physiolgenomics.00033.2009Cardioplegia is used to partially alleviate the effects of surgically induced global ischemia injury; however, the molecular mechanisms involved in this cardioprotection remain to be elucidated. To improve the understanding of the molecular processes modulating the effects of global ischemia and the cardioprotection afforded by cardioplegia, we constructed rabbit heart cDNA libraries and isolated, sequenced, and identified a compendium of nonredundant cDNAs for use in transcriptomic and proteomic analyses. New Zealand White rabbits were used to compare the effects of global ischemia and cardioplegia compared with control (nonischemic) hearts. The effects of RNA and protein synthesis on the cardioprotection afforded by cardioplegia were investigated separately by preperfusion with either ␣-amanitin or cycloheximide. Our results demonstrate that cardioplegia partially ameliorates the effects of global ischemia and that the cardioprotection is modulated by RNA-and protein-dependent mechanisms. Transcriptomic and proteomic enrichment analyses indicated that global ischemia downregulated genes/proteins associated with mitochondrial function and energy production, cofactor catabolism, and the generation of precursor metabolites of energy. In contrast, cardioplegia significantly increased differentially expressed genes/proteins associated with the mitochondrion and mitochondrial function and significantly upregulated the biological processes of muscle contraction, involuntary muscle contraction, carboxylic acid and fatty acid catabolic processes, fatty acid ␤-oxidation, and fatty acid metabolic processes. mitochondrion; ischemia-reperfusion MYOCARDIAL ISCHEMIA-REPERFUSION INJURY occurs as the result of the attenuation or cessation of coronary blood flow such that oxygen delivery to the myocardium is insufficient to meet energy demands. The cessation of myocardial coronary blood flow induces a cascade of cellular events that rapidly alter myocardial cellular homeostasis, leading to cellular dysfunction and/or death and postischemic functional impairment (23).To alleviate the effects of surgically induced ischemia/ reperfusion injury, surgeons use cardioplegia (CP) solutions that allow for the rapid electromechanical arrest of the myocardium through the alteration of cellular electrochemical gradients (40). In a series of studies, we have shown that magnesium-supplemented potassium CP with the addition of diazoxide significantly decreases myocardial cell death and significantly enhances postischemic functional recovery (22,40,43).The mechanisms through which CP affords cardioprotection are complex and cannot be investigated as a single entity; rather, they must be investigated as a system. In previous reports, we and others have used a variety of methods to identify the RNAs and proteins associated with global ischemia (GI) a...

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Section: Resultscontrasting

confidence: 44%

Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart

McCully

Bhasin

Daly

et al. 2009

Physiological Genomics

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“…They have usually compared gene expression between opposing pairs of samples, such as non-failing vs failing hearts, [53][54][55][56][57][58][59] ischemic vs non-ischemic hearts, 53,60 hypertrophic vs failing hearts, 61 atria vs ventricles 62 or male vs female failing hearts. 65 Gene Expression Profile of DCM Yang et al 53 performed microarray analysis of 4 human myocardial samples harvested from 2 patients without HF, 1 patient with DCM and 1 patient with ischemic cardiomyopathy (ICM) using the Affymetrix Hu6800 GeneChip microarray.…”

Section: Microarray Analysis Of the Failing Myocardiummentioning

confidence: 99%

“…Ellighaus et al 62 analyzed gene expression in human left atrial and ventricular myocardium from 6 patients with HF undergoing heart transplantation and identified 125 genes that were differentially expressed between the left atrial and ventricular myocardium among 22,215 genes on the Affymetrix GeneChip HG-U133A microarray. They found that several potassium channels, including TWIK-1, TASK-1, and Kv1.5, were more highly expressed in the atrium than in the ventricle of HF patients, whereas they observed higher expression of potassium channel Kir2.1 in the ventricle than in the atrium.…”

Section: Chamber-specific Gene Expressionmentioning

confidence: 99%

Global Gene Expression Profiling in the Failing Myocardium

Asakura

Kitakaze

2009

Circ J

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Heart failure (HF) is a syndrome that involves multiple cellular mechanisms leading to a common phenotype of reduced ventricular contraction and cardiac chamber dilation. To clarify the mechanisms, a number of microarray analyses of the failing myocardium have been conducted. Gene expression profiles are usually compared between opposing pairs of samples, such as non-failing vs failing hearts, ischemic vs non-ischemic hearts, male vs female failing hearts or atria vs ventricles of failing hearts. Apart from these conventional methods, a different novel approach identified cardiac myosin light chain kinase (MLCK) as a HF-related gene by the comprehensive search for the genes that had an expression level that strongly correlated with the severity of HF; further investigations proved the important role of cardiac MLCK in HF. Moreover, a robust gene expression signature composed of 27 genes was revealed on analysis of 4 independent microarray data sets from the failing myocardium of dilated cardiomyopathy. The authors newly demonstrate 107 HF-related genes that were listed in 2 or more of 7 microarray data sets previously reported. Among these genes, many were observed to be involved in mitochondrial dysfunction and oxidative phosphorylation and 3 extracellular molecules, including periostin, pleiotrophin, and SERPINA3, which might become novel diagnostic and therapeutic targets for HF. These novel strategies warrant the new identification of specific genes that are linked to the pathophysiology of HF. (Circ J 2009; 73: 1568 -1576

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“…Real-time polymerase chain reaction was performed as described previously. 25 Primer and probe sequences are given in the Table. Cycle threshold values were corrected for ribosomal protein L32, ␤-2 microglobulin, and ␤-actin mRNA levels to exclude different starting amounts of total RNA. We observed that the calculated expression level was independent of the housekeeping gene used (ribosomal protein L32, ␤-2 microglobulin, or ␤-actin) in RV samples or between treated and untreated H9c2 cells.…”

Section: Rna Extraction and Quantitative Real-time Polymerase Chain Rmentioning

confidence: 99%

Combined Tyrosine and Serine/Threonine Kinase Inhibition by Sorafenib Prevents Progression of Experimental Pulmonary Hypertension and Myocardial Remodeling

et al. 2008

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Background-Inhibition of tyrosine kinases, including platelet-derived growth factor receptor, can reduce pulmonary arterial pressure in experimental and clinical pulmonary hypertension. We hypothesized that inhibition of the serine/threonine kinases Raf-1 (also termed c-Raf) and b-Raf in addition to inhibition of tyrosine kinases effectively controls pulmonary vascular and right heart remodeling in pulmonary hypertension. Methods and Results-We investigated the effects of the novel multikinase inhibitor sorafenib, which inhibits tyrosine kinases as well as serine/threonine kinases, in comparison to imatinib, a tyrosine kinase inhibitor, on hemodynamics, pulmonary and right ventricular (RV) remodeling, and downstream signaling in experimental pulmonary hypertension. Fourteen days after monocrotaline injection, male rats were treated orally for another 14 days with sorafenib (10 mg/kg per day), imatinib (50 mg/kg per day), or vehicle (nϭ12 to 16 per group). RV systolic pressure was decreased to 35.0Ϯ1.5 mm Hg by sorafenib and to 54.0Ϯ4.4 mm Hg by imatinib compared with placebo (82.9Ϯ6.0 mm Hg). In parallel, both sorafenib and imatinib reduced RV hypertrophy and pulmonary arterial muscularization. The effects of sorafenib on RV systolic pressure and RV mass were significantly greater than those of imatinib. Sorafenib prevented phosphorylation of Raf-1 and suppressed activation of the downstream ERK1/2 signaling pathway in RV myocardium and the lungs. In addition, sorafenib but not imatinib antagonized vasopressin-induced hypertrophy of the cardiomyoblast cell line H9c2. Conclusions-The multikinase inhibitor sorafenib prevents pulmonary remodeling and improves cardiac and pulmonary function in experimental pulmonary hypertension. Sorafenib exerts direct myocardial antihypertrophic effects, which appear to be mediated via inhibition of the Raf kinase pathway. The combined inhibition of tyrosine and serine/threonine kinases may provide an option to treat pulmonary arterial hypertension and associated right heart remodeling.

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Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays

Cited by 100 publications

References 22 publications

Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart

Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart

Global Gene Expression Profiling in the Failing Myocardium

Combined Tyrosine and Serine/Threonine Kinase Inhibition by Sorafenib Prevents Progression of Experimental Pulmonary Hypertension and Myocardial Remodeling

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