title: Alterations in cardiac function and gene expression during autoimmune myocarditis in mice.
abstract: Although myocarditis has been implicated in the pathogenesis of heart failure, a definitive relationship between myocardial inflammation, cardiac dysfunction, and changes in myocyte gene expression has not been established. In this study, we examined the hypothesis that myocardial inflammation and replacement fibrosis following an autoimmune response can progress to cardiac dysfunction and may result in progression to the heart failure phenotype. SWXJ mice were immunized with cardiac myosin on day 0 and day 7, in order to induce an autoimmune response to the myosin protein. Cardiac catheterization via the right carotid artery was performed on days 14, 21, 28, 35, and 42, using a 1.4F Millar transducer-tipped catheter. Hearts were weighed, and cross-sections were cut and stained with either haematoxylin and eosin or Masson's trichrome, in order to identify areas of inflammation and/or fibrosis. Myocardial gene expression was determined by Northern blot analysis. In mice with histological evidence of myocarditis, the heart weight/body weight ratio increased beginning on day 14, and cardiac function decreased beginning on day 21. Myocardial inflammation was accompanied by significant fibrosis beginning on day 21. Quantitation of mRNA showed expression of ventricular atrial naturietic factor, as well as a decrease in myosin heavy chain alpha, beginning on day 21. These data demonstrate that autoimmune inflammation of the heart results in significant cardiac dysfunction, leading to phenotypic alterations similar to those demonstrated in human heart failure and animal models of heart failure.
authors.affiliation: Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Stull
authors.forename: N A
authors.initials: NA
authors.lastname: DiIulio
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.forename: C F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: N B
authors.initials: NB
authors.lastname: Ratliff
authors.forename: V K
authors.initials: VK
authors.lastname: Tuohy
authors.forename: C S
authors.initials: CS
authors.lastname: Moravec
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000503:physiopathology*; D001835:Body Weight; D004719:Endomyocardial Fibrosis / Q000209:etiology / Q000235:genetics; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D020409:Molecular Motor Proteins; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009205:Myocarditis / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D009218:Myosins / Q000276:immunology; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology
chemical_list: D001324:Autoantigens; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains; D009218:Myosins