Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays

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

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Background - Failing human hearts are characterized by altered cytoskeletal and myofibrillar, impaired signal transduction, abnormal protein turnover, and impaired energy metabolism. Thus, expression of multiple classes of genes is likely to be altered in human heart failure. Methods and Results - We used high-density oligonucleotide arrays to explore changes in expression of ≃7000 genes in 2 nonfailing and 2 failing human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy, respectively. We report altered expression of (1) cytoskeletal and myofibrillar genes (striated musicle. LIM protein-1 [SLIM1], myomesin, nonsarcomeric myosin regulatory light chain-2 [MLC2], and β-actin); (2) genes responsible for degradation and disassembly of myocardial proteins (α1-antichymotrypsin, ubiquitin, and gelsolin); (3) genes involved in metabolism (ATP synthase α-subunit, succinate dehydrogenase flavoprotein [SDH Fp] subunit, aldose reductase, and TIM17 preprotein translocase); (4) genes responsible for protein synthesis (elongation factor-2 [EF-2], eukaryotic initiation factor-4AII, and transcription factor homologue-HBZ17); and (5) genes encoding stress proteins (αB-crystallin and μ-crystallin). In 5 additional failing hearts and 4 additional nonfailing controls, we then compared expression of proteins encoded by the differentially expressed genes, αB-crystallin, SLIM1, gelsolin, α1-antichymotrypsin, and ubiquitin. In each case, changes in protein expression were consistent with changes in trancript measured by microarray analysis. Gelsolin protein expression was also increased in cardiomyopathic hearts from tropomodulin-overexpressing (TOT) mice and rac1-expressing (racET) mice. Conclusions - 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.

Original languageEnglish (US)
Pages (from-to)3046-3052
Number of pages7
JournalCirculation
Volume102
Issue number25
DOIs
StatePublished - Dec 19 2000
Externally publishedYes

Fingerprint

Gelsolin
Oligonucleotide Array Sequence Analysis
Crystallins
Genes
Proteins
Ubiquitin
Tropomodulin
Heart Failure
Peptide Elongation Factor 2
Connectin
Eukaryotic Initiation Factors
Gene Expression
Flavoproteins
Aldehyde Reductase
Myosin Light Chains
Succinate Dehydrogenase
Dilated Cardiomyopathy
Microarray Analysis
Heat-Shock Proteins
Energy Metabolism

Keywords

  • Cardiomyopathy
  • Gene expression
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. / Yang, Jiacheng; Moravec, Christine S.; Sussman, Mark A.; DiPaola, Nicholas R.; Fu, Dechen; Hawthorn, Lesleyann; Mitchell, Christina A.; Young, James B.; Francis, Gary S.; McCarthy, Patrick M.; Bond, Meredith.

In: Circulation, Vol. 102, No. 25, 19.12.2000, p. 3046-3052.

Research output: Contribution to journalArticle

Yang, J, Moravec, CS, Sussman, MA, DiPaola, NR, Fu, D, Hawthorn, L, Mitchell, CA, Young, JB, Francis, GS, McCarthy, PM & Bond, M 2000, 'Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays', Circulation, vol. 102, no. 25, pp. 3046-3052. https://doi.org/10.1161/01.CIR.102.25.3046
Yang, Jiacheng ; Moravec, Christine S. ; Sussman, Mark A. ; DiPaola, Nicholas R. ; Fu, Dechen ; Hawthorn, Lesleyann ; Mitchell, Christina A. ; Young, James B. ; Francis, Gary S. ; McCarthy, Patrick M. ; Bond, Meredith. / Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. In: Circulation. 2000 ; Vol. 102, No. 25. pp. 3046-3052.
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abstract = "Background - Failing human hearts are characterized by altered cytoskeletal and myofibrillar, impaired signal transduction, abnormal protein turnover, and impaired energy metabolism. Thus, expression of multiple classes of genes is likely to be altered in human heart failure. Methods and Results - We used high-density oligonucleotide arrays to explore changes in expression of ≃7000 genes in 2 nonfailing and 2 failing human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy, respectively. We report altered expression of (1) cytoskeletal and myofibrillar genes (striated musicle. LIM protein-1 [SLIM1], myomesin, nonsarcomeric myosin regulatory light chain-2 [MLC2], and β-actin); (2) genes responsible for degradation and disassembly of myocardial proteins (α1-antichymotrypsin, ubiquitin, and gelsolin); (3) genes involved in metabolism (ATP synthase α-subunit, succinate dehydrogenase flavoprotein [SDH Fp] subunit, aldose reductase, and TIM17 preprotein translocase); (4) genes responsible for protein synthesis (elongation factor-2 [EF-2], eukaryotic initiation factor-4AII, and transcription factor homologue-HBZ17); and (5) genes encoding stress proteins (αB-crystallin and μ-crystallin). In 5 additional failing hearts and 4 additional nonfailing controls, we then compared expression of proteins encoded by the differentially expressed genes, αB-crystallin, SLIM1, gelsolin, α1-antichymotrypsin, and ubiquitin. In each case, changes in protein expression were consistent with changes in trancript measured by microarray analysis. Gelsolin protein expression was also increased in cardiomyopathic hearts from tropomodulin-overexpressing (TOT) mice and rac1-expressing (racET) mice. Conclusions - 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.",
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T1 - Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays

AU - Yang, Jiacheng

AU - Moravec, Christine S.

AU - Sussman, Mark A.

AU - DiPaola, Nicholas R.

AU - Fu, Dechen

AU - Hawthorn, Lesleyann

AU - Mitchell, Christina A.

AU - Young, James B.

AU - Francis, Gary S.

AU - McCarthy, Patrick M.

AU - Bond, Meredith

PY - 2000/12/19

Y1 - 2000/12/19

N2 - Background - Failing human hearts are characterized by altered cytoskeletal and myofibrillar, impaired signal transduction, abnormal protein turnover, and impaired energy metabolism. Thus, expression of multiple classes of genes is likely to be altered in human heart failure. Methods and Results - We used high-density oligonucleotide arrays to explore changes in expression of ≃7000 genes in 2 nonfailing and 2 failing human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy, respectively. We report altered expression of (1) cytoskeletal and myofibrillar genes (striated musicle. LIM protein-1 [SLIM1], myomesin, nonsarcomeric myosin regulatory light chain-2 [MLC2], and β-actin); (2) genes responsible for degradation and disassembly of myocardial proteins (α1-antichymotrypsin, ubiquitin, and gelsolin); (3) genes involved in metabolism (ATP synthase α-subunit, succinate dehydrogenase flavoprotein [SDH Fp] subunit, aldose reductase, and TIM17 preprotein translocase); (4) genes responsible for protein synthesis (elongation factor-2 [EF-2], eukaryotic initiation factor-4AII, and transcription factor homologue-HBZ17); and (5) genes encoding stress proteins (αB-crystallin and μ-crystallin). In 5 additional failing hearts and 4 additional nonfailing controls, we then compared expression of proteins encoded by the differentially expressed genes, αB-crystallin, SLIM1, gelsolin, α1-antichymotrypsin, and ubiquitin. In each case, changes in protein expression were consistent with changes in trancript measured by microarray analysis. Gelsolin protein expression was also increased in cardiomyopathic hearts from tropomodulin-overexpressing (TOT) mice and rac1-expressing (racET) mice. Conclusions - 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.

AB - Background - Failing human hearts are characterized by altered cytoskeletal and myofibrillar, impaired signal transduction, abnormal protein turnover, and impaired energy metabolism. Thus, expression of multiple classes of genes is likely to be altered in human heart failure. Methods and Results - We used high-density oligonucleotide arrays to explore changes in expression of ≃7000 genes in 2 nonfailing and 2 failing human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy, respectively. We report altered expression of (1) cytoskeletal and myofibrillar genes (striated musicle. LIM protein-1 [SLIM1], myomesin, nonsarcomeric myosin regulatory light chain-2 [MLC2], and β-actin); (2) genes responsible for degradation and disassembly of myocardial proteins (α1-antichymotrypsin, ubiquitin, and gelsolin); (3) genes involved in metabolism (ATP synthase α-subunit, succinate dehydrogenase flavoprotein [SDH Fp] subunit, aldose reductase, and TIM17 preprotein translocase); (4) genes responsible for protein synthesis (elongation factor-2 [EF-2], eukaryotic initiation factor-4AII, and transcription factor homologue-HBZ17); and (5) genes encoding stress proteins (αB-crystallin and μ-crystallin). In 5 additional failing hearts and 4 additional nonfailing controls, we then compared expression of proteins encoded by the differentially expressed genes, αB-crystallin, SLIM1, gelsolin, α1-antichymotrypsin, and ubiquitin. In each case, changes in protein expression were consistent with changes in trancript measured by microarray analysis. Gelsolin protein expression was also increased in cardiomyopathic hearts from tropomodulin-overexpressing (TOT) mice and rac1-expressing (racET) mice. Conclusions - 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.

KW - Cardiomyopathy

KW - Gene expression

KW - Heart failure

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