title: Apolipoprotein J/clusterin induction in myocarditis: A localized response gene to myocardial injury.
abstract: The function of apolipoprotein J (apoJ) is unknown, but it has been hypothesized to be cytoprotective. In the normal heart, abundant apoJ mRNA and protein are expressed in atrial myocytes; no expression is detected in ventricular myocytes. To provide clues about the role of apoJ in the heart, the response of apoJ to heart disease, including three models of myocarditis and two models of in vivo pressure overload hypertrophy, were examined. In the disease model studied extensively, myosin-induced myocarditis, in situ hybridization detected induction of apoJ mRNA in ventricular myocytes immediately before histological evidence of injury. ApoJ message in ventricular myocytes reached high levels as myocarditis became more severe. Evidence of early apoJ induction, before inflammation and injury, also occurred in viral myocarditis. ApoJ mRNA was not present in the inflammatory or interstitial cells during myocarditis. In areas of severe inflammation and myocardial fiber degeneration, apoJ showed a gradient of expression, with highest levels in myocytes immediately surrounding the lesion and diminishing with increasing distance. ApoJ protein also accumulated in myocytes at the interface between degenerated myocardial tissue and the surrounding cardiac tissue. During cardiac hypertrophy that occurred without associated inflammation or cell damage, ventricular apoJ mRNA was not detected. When ischemic damage accompanied hypertrophy, apoJ was induced in the ventricular myocytes near the lesion borders. The correlation of apoJ induction with ventricular tissue damage, but not hypertrophy, suggests that apoJ is a repair response protein. We propose that apoJ functions to limit tissue injury and/or promote tissue remodeling.
authors.affiliation: Developmental Biology Graduate Program, University of Cincinnati, College of Medicine, Cincinnati, 45267, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Swertfeger
authors.forename: D P
authors.initials: DP
authors.lastname: Witte
authors.forename: W D
authors.initials: WD
authors.lastname: Stuart
authors.forename: H A
authors.initials: HA
authors.lastname: Rockman
authors.forename: J A
authors.initials: JA
authors.lastname: Harmony
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000096:biosynthesis*; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D029822:Enterovirus B, Human; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones; D009205:Myocarditis / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C495243:Clu protein, mouse; D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger