Decreased SLIM1 Expression and Increased Gelsolin Expression in Failing Human Hearts Measured by High-Density Oligonucleotide Arrays

Yang, Jie; Moravec, Christine S.; Sussman, Mark A.; DiPaola, Nicholas R.; Fu, Dianzheng; Hawthorn, Lesleyann; Mitchell, Christina A.; Young, James B.; Francis, Gary S.; McCarthy, Patrick M.; Bond, Meredith

doi:10.1161/01.cir.102.25.3046

Cited by 203 publications

(129 citation statements)

References 28 publications

(25 reference statements)

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“…Age, medication, and an index of cardiac function (left ventricular ejection fraction) were obtained (Table 1). Tissue handling was as described (2,5). Total RNA was isolated from the myocardium by using TRIzol reagent (GIBCO͞BRL) as described by the manufacturer.…”

Section: Materials and Methods Mrna Preparation And Hybridization To mentioning

confidence: 99%

“…Detailed protocols for data extraction from Affymetrix oligonucleotide arrays and documentation on the sensitivity and quantitative aspects of the method have been described (2,8). Affymetrix HuFl 6800 GeneChips containing 6,606 unique genes were used in this study with one GeneChip used for each human heart sample.…”

Section: Materials and Methods Mrna Preparation And Hybridization To mentioning

confidence: 99%

“…However, multiple molecular pathways are believed responsible for transducing these stimuli into changes in gene expression during the process of heart failure. Microarrays can provide an effective platform to examine these pathways in terms of mRNA expression (2).…”

mentioning

confidence: 99%

“…Attempts using oligonucleotide (2) and cDNA (3) arrays have previously been made to identify genes differentially expressed in failing (F) and nonfailing (NF) human hearts. In a previous study from our laboratory (2), two NF donor hearts and two F human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy (DCM), respectively, were studied, and 19 genes were reported to be differentially expressed.…”

mentioning

confidence: 99%

“…In a previous study from our laboratory (2), two NF donor hearts and two F human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy (DCM), respectively, were studied, and 19 genes were reported to be differentially expressed. Using a cardiovascular specific cDNA microarray, Barrans and colleagues examined two normal adult and two human hearts with diagnosis of hypertrophic cardiomyopathy.…”

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confidence: 99%

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The gene expression fingerprint of human heart failure

Tan

Moravec

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Multiple pathways are responsible for transducing mechanical and hormonal stimuli into changes in gene expression during heart failure. In this study our goals were (i) to develop a sound statistical method to establish a comprehensive cutoff point for identification of differentially expressed genes, (ii) to identify a gene expression fingerprint for heart failure, (iii) to attempt to distinguish different etiologies of heart failure by their gene expression fingerprint, and (iv) to identify gene clusters that show coordinated up-or downregulation in human heart failure. We used oligonucleotide microarrays to profile seven nonfailing (NF) and eight failing (F) human hearts with a diagnosis of end-stage dilated cardiomyopathy. Biological and experimental variability of the hybridization data were analyzed, and then a statistical analysis procedure was developed, including Student's t test after log-transformation and Wilcoxon Mann-Whitney test. A comprehensive cutoff point composed of fold change, average difference, and absolute call was then established and validated by TaqMan PCR. Of 6,606 genes on the GeneChip, 103 genes in 10 functional groups were differentially expressed between F and NF hearts. A dendrogram identified a gene expression fingerprint of F and NF hearts and also distinguished two F hearts with distinct etiologies (familial and alcoholic cardiomyopathy, respectively) with different expression patterns. K means clustering also revealed two potentially novel pathways associated with up-regulation of atrial natriuretic factor and brain natriuretic peptide and with increased expression of extracellular matrix proteins. Gene expression fingerprints may be useful indicators of heart failure etiologies.

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Section: Materials and Methods Mrna Preparation And Hybridization To mentioning

confidence: 99%

Section: Materials and Methods Mrna Preparation And Hybridization To mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The gene expression fingerprint of human heart failure

Tan

Moravec

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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238

196

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Overview of Microarrays in Genomic Analysis

Burgess

2004

Molecular Analysis and Genome Discovery

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Heart failure and apoptosis: Electrophoretic methods support data from micro- and macro-arrays. A critical review of genomics and proteomics

et al. 2001

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The multiple causes and multiple consequences of mammalian heart failure make it an attractive proposition for analysis using gene array technology, especially where the failure is idiopathic in nature. However, gene arrays also hold potential artefacts, particularly when gene expression levels are low, and where changes in expression levels are modest. Also, at present, the number of genes available on arrays is not large enough to prevent potential sampling deficiencies. Thus, it may not be wise to place too much reliance on quantitative interpretations of gene array data. Also, recently doubts were raised about the qualitative reliability of array genes. Electrophoretic methods are slow, cumbersome and complex but they can provide confirmation that the trends and numbers arising from the new gene arrays are reliable. In this overview, we compare gene array data with data from protein activity assays such as zymograms, Western blots, two-dimensional electrophoresis, and immunohistochemistry. Similar or complementary data from the same heart tissues analyzed by either microarrays or macroarrays can be reassuring to those interested in reliable molecular analyses of normal and failing hearts. Similar principles will apply to other tissues and cells.

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Decreased SLIM1 Expression and Increased Gelsolin Expression in Failing Human Hearts Measured by High-Density Oligonucleotide Arrays

Abstract: Altered expression of the genes identified in this study may contribute to development of the heart failure phenotype and/or represent compensatory mechanisms to sustain cardiac function in failing human hearts.

Cited by 203 publications

References 28 publications

The gene expression fingerprint of human heart failure

The gene expression fingerprint of human heart failure

Overview of Microarrays in Genomic Analysis

Heart failure and apoptosis: Electrophoretic methods support data from micro- and macro-arrays. A critical review of genomics and proteomics

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