title: Abundant apoptosis in nutmeg liver of cardiomyopathic hamsters. Apoptotic cell death as a possible mechanism of hepatic remodeling by congestion.
abstract: Chronic congestive heart failure (CHF) causes structural remodeling of the liver, generally leading to nutmeg liver. Male UM-X7.1 hamsters, a strain developing cardiomyopathy, had no CHF and decompensated CHF (n = 6 each) at the age of 10 and 30 weeks, respectively. We used age-matched, male Syrian hamsters without CHF (n = 6 each) as controls. All the 30-week-old UM-X7.1 hamsters had a typical nutmeg liver in which the population of hepatocytes was decreased. Positive in situ nick end labeling (TUNEL) was found in 2.2 +/- 0.74% of hepatocytes in congestive livers, being significantly higher compared with the other groups without CHF (< 0.5%). DNA ladder pattern was also evident in the congestive livers. Electron microscopy revealed a typical apoptotic ultrastructure in the hepatocytes of the 30-week-old UM-X7.1 hamsters. However, many showed secondary necrotic changes. Although hepatocytes undergoing oncosis (primary necrosis) are rare, they were also found. The level of soluble Fas ligand in the plasma was increased, and Fas receptor in the liver was overexpressed in the CHF animals. In addition, both the Bax/Bcl-2 ratio and the Bad/Bcl-xL ratio were increased, and caspase-3 was activated in them. Our findings suggest that hepatocyte apoptosis contributes to hepatic remodeling under conditions of CHF.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kawase
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Kenji
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koda
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Motoo
authors.initials: M
authors.lastname: Kanoh
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kunishima
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohkusa
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000151:congenital / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D006224:Cricetinae; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure*; D020287:In Situ Nick-End Labeling; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D008854:Microscopy, Electron; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051020:bcl-X Protein; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; D053148:Caspase 3; D020169:Caspases