title: Virus-induced dilated cardiomyopathy is characterized by increased levels of fibrotic extracellular matrix proteins and reduced amounts of energy-producing enzymes.
abstract: The most relevant clinical phenotype resulting from chronic enteroviral myocarditis is dilated cardiomyopathy (DCM). Mice of the susceptible mouse strain A.BY/SnJ mimick well human DCM since they develop as a consequence of persistent infection and chronic inflammation a dilation of the heart ventricle several weeks after coxsackievirus B3 (CVB3) infection. Therefore, this model is well suited for the analysis of changes in the heart proteome associated with DCM. Here, we present a proteomic survey of the dilated hearts based on differential fluorescence gel electrophoresis and liquid chromatography-mass spectrometric centered methods in comparison to age-matched non-infected hearts. In total, 101 distinct proteins, which belong to categories immunity and defense, cell structure and associated proteins, energy metabolism and protein metabolism/modification differed in their levels in both groups. Levels of proteins involved in fatty acid metabolism and electron transport chain were found to be significantly reduced in infected mice suggesting a decrease in energy production in CVB3-induced DCM. Furthermore, proteins associated with muscle contraction (MLRV, MLRc2, MYH6, MyBPC3), were present in significantly altered amounts in infected mice. A significant increase in the level of extracellular matrix proteins in the dilated hearts indicates cardiac remodeling due to fibrosis.
authors.affiliation: Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
authors.forename: Krishnatej
authors.initials: K
authors.lastname: Nishtala
authors.forename: Truong Q
authors.initials: TQ
authors.lastname: Phong
authors.forename: Leif
authors.initials: L
authors.lastname: Steil
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Heyo K
authors.initials: HK
authors.lastname: Kroemer
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003384:Coxsackievirus Infections / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism; D029822:Enterovirus B, Human / Q000302:isolation & purification*; D004798:Enzymes / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D051379:Mice; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D015203:Reproducibility of Results; D020257:Ventricular Remodeling
chemical_list: D004798:Enzymes; D016326:Extracellular Matrix Proteins; D020543:Proteome