title: Functional proteomic analysis of experimental autoimmune myocarditis-induced chronic heart failure in the rat.
abstract: 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.
authors.affiliation: Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Niigata University, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sanzen
authors.forename: Minami
authors.initials: M
authors.lastname: Ito
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ohta
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Tomie
authors.initials: T
authors.lastname: Kawada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D009205:Myocarditis / Q000150:complications / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics; D051381:Rats; D011917:Rats, Inbred Lew; D012995:Solubility
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D011506:Proteins; D020543:Proteome