TY - JOUR
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, Lesley
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
UR - http://www.scopus.com/inward/record.url?scp=0034687593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034687593&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.102.25.3046
DO - 10.1161/01.CIR.102.25.3046
M3 - Article
C2 - 11120693
AN - SCOPUS:0034687593
SN - 0009-7322
VL - 102
SP - 3046
EP - 3052
JO - Circulation
JF - Circulation
IS - 25
ER -