Functional proteomic analysis of experimental autoimmune myocarditis-induced chronic heart failure in the rat.

Experimental autoimmune myocarditis (EAM)-induced heart failure in rats is used to study the pathogenesis of heart failure. Based on a proteomic analysis of soluble (S) and membranous (M) fractions extracted from ventricles of rats with a stable chronic form of EAM-induced heart failure, we assessed changes in protein levels and their correlation to heart functions to gain insights into the pathogenesis and to explore new targets for the treatment of heart failure. Proteins were separated by two-dimensional gel electrophoresis and silver stained spots were analyzed. In the S-fraction, 274+/-3 spots were detected in the normal (N)-group and 273+/-6 in the heart failure (HF)-group. In the HF-group, 26 of the spots were increased and 15 were decreased in intensity. In the M-fraction, 277+/-3 spots were detected in the N-group and 277+/-2 in the HF-group, with 20 spots increased and 10 decreased in intensity. We analyzed relationships between the expression of these proteins and 11 parameters of heart function, and found all the significantly changed spots to correlate with at least one of the parameters. We analyzed 49 spots that correlated with over 9 parameters of heart function using mass spectrometry, and identified 15 as proteins with increased expression including glucose regulated protein (GRP)78, an endoplasmic-stress related protein, and heat shock protein (HSP)90beta, a molecular chaperone, and 4 spots as proteins with decreased expression. It is suggested that in the heart failure model, GRP78 and HSP90beta play a role in the protection or deterioration of the heart and may be new targets for treatment.

[1]  Kenichi Watanabe,et al.  Long-term Carperitide Treatment Attenuates Left Ventricular Remodeling in Rats With Heart Failure After Autoimmune Myocarditis , 2009, Journal of cardiovascular pharmacology.

[2]  K. Shin‐ya,et al.  Preventing the unfolded protein response via aberrant activation of 4E‐binding protein 1 by versipelostatin , 2009, Cancer science.

[3]  Bo Xu,et al.  In-depth proteomic profiling of the normal human kidney glomerulus using two-dimensional protein prefractionation in combination with liquid chromatography-tandem mass spectrometry. , 2007, Journal of proteome research.

[4]  Amy S. Lee,et al.  ER chaperones in mammalian development and human diseases , 2007, FEBS letters.

[5]  Masahiro Ito,et al.  Cardioprotective effects of recombinant human erythropoietin in rats with experimental autoimmune myocarditis. , 2006, Biochemical and biophysical research communications.

[6]  M. Dunn,et al.  Proteomics of the Heart : Unraveling Disease , 2006 .

[7]  H. Sabbah,et al.  Expression of Cytoskeletal, Linkage and Extracellular Proteins in Failing Dog Myocardium , 2005, Heart Failure Reviews.

[8]  Melanie Y. White,et al.  Proteomics of ischemia/reperfusion injury in rabbit myocardium reveals alterations to proteins of essential functional systems , 2005, Proteomics.

[9]  K. Pritchard,et al.  Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat: role of nitric oxide synthase and Hsp90. , 2005, Journal of molecular and cellular cardiology.

[10]  A. Tsugita,et al.  Two‐dimensional electrophoretic profiling of normal human kidney glomerulus proteome and construction of an extensible markup language (XML)‐based database , 2005, Proteomics.

[11]  K. Murray,et al.  Rapid stimulation causes electrical remodeling in cultured atrial myocytes. , 2005, Journal of molecular and cellular cardiology.

[12]  S. Anker,et al.  Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival. , 2004, International journal of cardiology.

[13]  L. Hendershot,et al.  ER chaperone functions during normal and stress conditions , 2004, Journal of Chemical Neuroanatomy.

[14]  M. Hori,et al.  Prolonged Endoplasmic Reticulum Stress in Hypertrophic and Failing Heart After Aortic Constriction: Possible Contribution of Endoplasmic Reticulum Stress to Cardiac Myocyte Apoptosis , 2004, Circulation.

[15]  K. Ozawa,et al.  Translocation and cleavage of myocardial dystrophin as a common pathway to advanced heart failure: a scheme for the progression of cardiac dysfunction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  A. Goette,et al.  Proteomics in myocardial diseases. , 2004, Pathology, research and practice.

[17]  H. Yoshida,et al.  Induction of heat shock protein 72 in the failing heart is attenuated after an exposure to heat shock , 2004, Molecular and Cellular Biochemistry.

[18]  K. Tanonaka,et al.  [Induction of heat shock protein 70 in failing heart]. , 2004, Nihon yakurigaku zasshi. Folia pharmacologica Japonica.

[19]  L. Fritz,et al.  A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors , 2003, Nature.

[20]  Kenichi Watanabe,et al.  Effects of imidapril and TA-606 on rat dilated cardiomyopathy after myocarditis. , 2003, Japanese heart journal.

[21]  M. Kanaoka,et al.  Proteomic analysis of rat heart in ischemia and ischemia‐reperfusion using fluorescence two‐dimensional difference gel electrophoresis , 2003, Proteomics.

[22]  P. Jungblut,et al.  Separation and identification of human heart proteins. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[23]  J. Eaton,et al.  Molecular bases of cellular iron toxicity. , 2002, Free radical biology & medicine.

[24]  Hiroshi Sato,et al.  Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: Amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Kenichi Watanabe,et al.  Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy , 2000, British journal of pharmacology.

[26]  W. Schaper,et al.  Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium. , 2000, Circulation research.

[27]  J. Schaper,et al.  The role of the cytoskeleton in heart failure. , 2000, Cardiovascular research.

[28]  K P Pleissner,et al.  Proteomics in human disease: Cancer, heart and infectious diseases , 1999, Electrophoresis.

[29]  P. Csermely,et al.  Associate Editor: D. Shugar The 90-kDa Molecular Chaperone Family: Structure, Function, and Clinical Applications. A Comprehensive Review , 1998 .

[30]  D. Mann,et al.  Differential expression of heat shock proteins in normal and failing human hearts. , 1998, Journal of molecular and cellular cardiology.

[31]  H. Zimmer,et al.  The oxidative pentose phosphate pathway in the heart: Regulation, physiologicla significance, and clinical implications , 1992, Basic Research in Cardiology.

[32]  C. R. Wilson,et al.  Proteome analysis of isolated perfused organ effluent as a novel model for protein biomarker discovery. , 2006, Journal of proteome research.

[33]  J. Schaper,et al.  The extracellular matrix in the failing human heart. , 1992, Basic research in cardiology.