(Circulation. 2000;102:3046.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Decreased SLIM1 Expression and Increased Gelsolin Expression in Failing Human Hearts Measured by High-Density Oligonucleotide Arrays
From the Department of Molecular Cardiology (J.Y., M.B.), Molecular Biotechnology Core (L.H.), Center for Anesthesiology Research (C.S.M., N.R.D.), Lerner Research Institute, Cleveland, Ohio; Departments of Cardiology (J.B.Y., G.S.F.), Thoracic and Cardiovascular Surgery (P.M.M.), Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Physiology and Biophysics (C.S.M., M.B.), School of Medicine, Case Western Reserve University, Cleveland, Ohio; Division of Molecular Cardiovascular Biology (M.A.S., D.F.), Children’s Hospital Medical Center, Cincinnati, Ohio; and Department of Biochemistry and Molecular Biology, Monash University (C.A.M.), Melbourne, Australia.
Correspondence to Meredith Bond, PhD, Department of Molecular Cardiology NB50, Cleveland Clinic Foundation, Cleveland, OH 44195. E-mail bondm{at}ccf.org
Background—Failing human hearts are characterized by altered cytoskeletal and myofibrillar organization, 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 muscle LIM protein-1 [SLIM1], myomesin,
nonsarcomeric myosin regulatory light chain-2
[MLC2], and ß-actin); (2) genes responsible
for degradation and disassembly of myocardial proteins
(
1-antichymotrypsin, ubiquitin, and
gelsolin); (3) genes involved in metabolism (ATP synthase -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 (B-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, B-crystallin, SLIM1, gelsolin,
1-antichymotrypsin, and ubiquitin. In each
case, changes in protein expression were consistent with changes in
transcript 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.
Key Words: heart failure • cardiomyopathy • gene expression
This article has been cited by other articles:
 |
|
 |
|
  R. Sarwar and S. A. Cook Genomic Analysis of Left Ventricular Remodeling Circulation, August 4, 2009; 120(5): 437 - 444. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nishio and A. Matsumori Gelsolin and Cardiac Myocyte Apoptosis: A New Target in the Treatment of Postinfarction Remodeling Circ. Res., April 10, 2009; 104(7): 829 - 831. [Full Text] [PDF]
|
|
|
|
|
|
G. H. Li, Y. Shi, Y. Chen, M. Sun, S. Sader, Y. Maekawa, S. Arab, F. Dawood, M. Chen, G. De Couto, et al. Gelsolin Regulates Cardiac Remodeling After Myocardial Infarction Through DNase I-Mediated Apoptosis Circ. Res., April 10, 2009; 104(7): 896 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ruppert, T. Meyer, S. Pankuweit, E. Moller, R. C. Funck, W. Grimm, B. Maisch, and German Heart Failure Network Gene expression profiling from endomyocardial biopsy tissue allows distinction between subentities of dilated cardiomyopathy. J. Thorac. Cardiovasc. Surg., August 1, 2008; 136(2): 360 - 369.e1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, C. F. Browning, H. Hallaq, L. Yermalitskaya, J. Esker, M. R. Hall, A. J. Link, A.-J. L. Ham, M. J. McGrath, C. A. Mitchell, et al. Four and a half LIM protein 1: a partner for KCNA5 in human atrium Cardiovasc Res, June 1, 2008; 78(3): 449 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kaiserova, X.-L. Tang, S. Srivastava, and A. Bhatnagar Role of Nitric Oxide in Regulating Aldose Reductase Activation in the Ischemic Heart J. Biol. Chem., April 4, 2008; 283(14): 9101 - 9112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Haddad, L. J. Saunders, S. D. Crosby, M. Carles, F. del Monte, K. King, M. R. Bristow, F. G. Spinale, T. E. Macgillivray, M. J. Semigran, et al. Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences Physiol Genomics, April 1, 2008; 33(2): 267 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Bullard, T. L. Protack, F. Aguilar, S. Bagwe, H. T. Massey, and B. C. Blaxall Identification of Nogo as a novel indicator of heart failure Physiol Genomics, January 17, 2008; 32(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ojaimi, K. Qanud, T. H. Hintze, and F. A. Recchia Altered expression of a limited number of genes contributes to cardiac decompensation during chronic ventricular tachypacing in dogs Physiol Genomics, March 14, 2007; 29(1): 76 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schiekofer, I. Shiojima, K. Sato, G. Galasso, Y. Oshima, and K. Walsh Microarray analysis of Akt1 activation in transgenic mouse hearts reveals transcript expression profiles associated with compensatory hypertrophy and failure Physiol Genomics, October 11, 2006; 27(2): 156 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Donahue, D. A. Marchuk, and H. A. Rockman Redefining Heart Failure: The Utility of Genomics J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1289 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kaiserova, S. Srivastava, J. D. Hoetker, S. O. Awe, X.-L. Tang, J. Cai, and A. Bhatnagar Redox Activation of Aldose Reductase in the Ischemic Heart J. Biol. Chem., June 2, 2006; 281(22): 15110 - 15120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]
|
|
|
|
|
|
S. Demolombe, C. Marionneau, S. Le Bouter, F. Charpentier, and D. Escande Functional genomics of cardiac ion channel genes Cardiovasc Res, August 15, 2005; 67(3): 438 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cunha-Neto, V. J. Dzau, P. D. Allen, D. Stamatiou, L. Benvenutti, M. L. Higuchi, N. S. Koyama, J. S. Silva, J. Kalil, and C.-C. Liew Cardiac Gene Expression Profiling Provides Evidence for Cytokinopathy as a Molecular Mechanism in Chagas' Disease Cardiomyopathy Am. J. Pathol., August 1, 2005; 167(2): 305 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sanoudou, E. Vafiadaki, D. A. Arvanitis, E. Kranias, and A. Kontrogianni-Konstantopoulos Array lessons from the heart: focus on the genome and transcriptome of cardiomyopathies Physiol Genomics, April 14, 2005; 21(2): 131 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Steenman, G. Lamirault, N. Le Meur, M. Le Cunff, D. Escande, and J. J. Leger Distinct molecular portraits of human failing hearts identified by dedicated cDNA microarrays Eur J Heart Fail, March 2, 2005; 7(2): 157 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Mistry, A. Kato, Y. H. Tran, S. Honda, T. Tsukada, Y. Takei, and S. Hirose FHL5, a novel actin-binding protein, is highly expressed in eel gill pillar cells and responds to wall tension Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1141 - R1154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhao, A. Chow, J. Powers, G. Fajardo, and D. Bernstein Microarray analysis of gene expression after transverse aortic constriction in mice Physiol Genomics, September 16, 2004; 19(1): 93 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abu-Issa and M. L. Kirby Take Heart in the Age of "Omics" Circ. Res., August 20, 2004; 95(4): 335 - 336. [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Podgoreanu and D. A. Schwinn Genomics and the circulation Br. J. Anaesth., July 1, 2004; 93(1): 140 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tabibiazar, R. A. Wagner, A. Liao, and T. Quertermous Transcriptional Profiling of the Heart Reveals Chamber-Specific Gene Expression Patterns Circ. Res., December 12, 2003; 93(12): 1193 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. McGrath, C. A. Mitchell, I. D. Coghill, P. A. Robinson, and S. Brown Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces {alpha}5{beta}1-integrin-dependent myocyte elongation Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1513 - C1526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, R. Klevitsky, W. Huang, J. Glasford, F. Li, and J. Robbins {alpha}B-Crystallin Modulates Protein Aggregation of Abnormal Desmin Circ. Res., November 14, 2003; 93(10): 998 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Matsui, A. Saiura, Y. Sugawara, M. Sata, K. Naruse, H. Yagita, T. Kohro, C. Mataki, A. Izumi, T. Yamaguchi, et al. Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade Physiol Genomics, November 11, 2003; 15(3): 199 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. McGregor and M. J. Dunn Proteomics of heart disease Hum. Mol. Genet., October 15, 2003; 12(90002): R135 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Christopher, T. F. Mueller, R. DeFina, Y. Liang, J. Zhang, R. Gentleman, and D. L. Perkins The graft response to transplantation: a gene expression profile analysis Physiol Genomics, September 29, 2003; 15(1): 52 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Grzeskowiak, H. Witt, M. Drungowski, R. Thermann, S. Hennig, A. Perrot, K. J. Osterziel, D. Klingbiel, S. Scheid, R. Spang, et al. Expression profiling of human idiopathic dilated cardiomyopathy Cardiovasc Res, August 1, 2003; 59(2): 400 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Coghill, S. Brown, D. L. Cottle, M. J. McGrath, P. A. Robinson, H. H. Nandurkar, J. M. Dyson, and C. A. Mitchell FHL3 Is an Actin-binding Protein That Regulates {alpha}-Actinin-mediated Actin Bundling: FHL3 LOCALIZES TO ACTIN STRESS FIBERS AND ENHANCES CELL SPREADING AND STRESS FIBER DISASSEMBLY J. Biol. Chem., June 20, 2003; 278(26): 24139 - 24152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Napoli, L O Lerman, V Sica, A Lerman, G Tajana, and F de Nigris Microarray analysis: a novel research tool for cardiovascular scientists and physicians Heart, June 1, 2003; 89(6): 597 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kaynak, A. von Heydebreck, S. Mebus, D. Seelow, S. Hennig, J. Vogel, H.-P. Sperling, R. Pregla, V. Alexi-Meskishvili, R. Hetzer, et al. Genome-Wide Array Analysis of Normal and Malformed Human Hearts Circulation, May 20, 2003; 107(19): 2467 - 2474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Winslow and M. S. Boguski Genome Informatics: Current Status and Future Prospects Circ. Res., May 16, 2003; 92(9): 953 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Dos Remedios, D. Chhabra, M. Kekic, I. V. Dedova, M. Tsubakihara, D. A. Berry, and N. J. Nosworthy Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments Physiol Rev, April 1, 2003; 83(2): 433 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Mueller, C. Ma, J. A. Lederer, and D. L. Perkins Differentiation of stress, metabolism, communication, and defense responses following transplantation J. Leukoc. Biol., March 1, 2003; 73(3): 379 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Robinson, S. Brown, M. J. McGrath, I. D. Coghill, R. Gurung, and C. A. Mitchell Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration Am J Physiol Cell Physiol, March 1, 2003; 284(3): C681 - C695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Philip-Couderc, F. Smih, M. Pelat, C. Vidal, P. Verwaerde, A. Pathak, S. Buys, M. Galinier, J.-M. Senard, and P. Rouet Cardiac Transcriptome Analysis in Obesity-Related Hypertension Hypertension, March 1, 2003; 41(3): 414 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yun, M. J Zuscik, P. Gonzalez-Cabrera, D. F McCune, S. A Ross, R. Gaivin, M. T Piascik, and D. M Perez Gene expression profiling of {alpha}1b-adrenergic receptor-induced cardiac hypertrophy by oligonucleotide arrays Cardiovasc Res, February 1, 2003; 57(2): 443 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S Chugh, S. Whitesel, M. Turner, C. T Roberts Jr., and S. R Nagalla Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model Cardiovasc Res, February 1, 2003; 57(2): 477 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Steenman, Y.-W. Chen, M. Le Cunff, G. Lamirault, A. Varro, E. Hoffman, and J. J. Leger Transcriptomal analysis of failing and nonfailing human hearts Physiol Genomics, January 15, 2003; 12(2): 97 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Srivastava, B. Chandrasekar, A. Bhatnagar, and S. D. Prabhu Lipid peroxidation-derived aldehydes and oxidative stress in the failing heart: role of aldose reductase Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2612 - H2619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Cook and A. Rosenzweig DNA Microarrays: Implications for Cardiovascular Medicine Circ. Res., October 4, 2002; 91(7): 559 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fatkin and R. M. Graham Molecular Mechanisms of Inherited Cardiomyopathies Physiol Rev, October 1, 2002; 82(4): 945 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. PALINSKI and C. NAPOLI The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis FASEB J, September 1, 2002; 16(11): 1348 - 1360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Ramana, D. Chandra, S. Srivastava, A. Bhatnagar, B. B. Aggarwal, and S. K. Srivastava Aldose Reductase Mediates Mitogenic Signaling in Vascular Smooth Muscle Cells J. Biol. Chem., August 23, 2002; 277(35): 32063 - 32070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-L. Tan, C. S. Moravec, J. Li, C. Apperson-Hansen, P. M. McCarthy, J. B. Young, and M. Bond The gene expression fingerprint of human heart failure PNAS, August 20, 2002; 99(17): 11387 - 11392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, R. Bolli, S.-Q. Liu, X.-L. Tang, E. Kodani, Y.-t. Xuan, S. Srivastava, and A. Bhatnagar Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning Circ. Res., August 9, 2002; 91(3): 240 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. Hwang, P. D. Allen, G. C. Tseng, C.-W. Lam, L. Fananapazir, V. J. Dzau, and C.-C. Liew Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure Physiol Genomics, July 12, 2002; 10(1): 31 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Barrans, P. D. Allen, D. Stamatiou, V. J. Dzau, and C.-C. Liew Global Gene Expression Profiling of End-Stage Dilated Cardiomyopathy Using a Human Cardiovascular-Based cDNA Microarray Am. J. Pathol., June 1, 2002; 160(6): 2035 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.A Henriksen and Y Kotelevtsev Application of gene expression profiling to cardiovascular disease Cardiovasc Res, April 1, 2002; 54(1): 16 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Yamani, C. S. Masri, N. B. Ratliff, M. Bond, R. C. Starling, E. M. Tuzcu, P. M. McCarthy, and J. B. Young The role of vitronectin receptor ({alpha}v{beta}3) and tissue factor in the pathogenesis of transplant coronary vasculopathy J. Am. Coll. Cardiol., March 6, 2002; 39(5): 804 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Lee Functional Genomics and Cardiovascular Drug Discovery Circulation, September 18, 2001; 104(12): 1441 - 1446. [Full Text] [PDF]
|
|
|
|
|
|
M. W.M. Knaapen, M. J. Davies, M. De Bie, A. J. Haven, W. Martinet, and M. M. Kockx Apoptotic versus autophagic cell death in heart failure Cardiovasc Res, August 1, 2001; 51(2): 304 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Rao and M. Bond Microarrays : Managing the Data Deluge Circ. Res., June 22, 2001; 88(12): 1226 - 1227. [Full Text] [PDF]
|
|
|
|
|
|
M. D. Schneider and R. J. Schwartz Chips Ahoy : Gene Expression in Failing Hearts Surveyed by High-Density Microarrays Circulation, December 19, 2000; 102(25): 3026 - 3027. [Full Text] [PDF]
|
|
|
|
|
|
M. H. Yamani, E. M. Tuzcu, R. C. Starling, N. B. Ratliff, Y. Yu, D. G. Vince, K. Powell, D. Cook, P. McCarthy, and J. B. Young Myocardial Ischemic Injury After Heart Transplantation Is Associated With Upregulation of Vitronectin Receptor ({alpha}v{beta}3), Activation of the Matrix Metalloproteinase Induction System, and Subsequent Development of Coronary Vasculopathy Circulation, April 23, 2002; 105(16): 1955 - 1961. [Abstract] [Full Text] [PDF]
|
|