title: Autophagic degeneration and death of cardiomyocytes in heart failure.
abstract: Numerous cardiomyocytes were found to show autophagic vacuolar degeneration in the UM-X7.1 hamster model of human dilated cardiomyopathy, and autophagy-related proteins--i.e., ubiquitin, cathepsin D and Rab7--were upregulated in those hearts. Importantly, Evans blue-positive cardiomyocytes with leaky plasma membranes were also positive for cathepsin D, suggesting a link between autophagic degeneration and cell death. Treatment with granulocyte colony-stimulating factor (G-CSF) significantly improved survival, cardiac function and remodeling in these animals, and such beneficial effects were accompanied by a reduction in autophagy, an increase in cardiomyocyte size, and a reduction in myocardial fibrosis. G-CSF-induced changes in molecular signaling included activation of Akt and Stat3 (signal transducer and activator of transcription-3), a reduction in the level of myocardial tumor necrosis factor-alpha, and an increase in those of matrix metalloproteinases. In contrast, neither cardiomyocyte apoptosis nor regeneration of cardiomyocytes from bone marrow-derived cells was significant. It thus appears that autophagic death and autophagy-dependent degeneration are important contributors to loss of cardiomyocyte function in the cardiomyopathic hamster and that G-CSF exerts a beneficial effect, mainly via an anti-autophagic mechanism.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Shusaku
authors.initials: S
authors.lastname: Miyata
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kawase
authors.forename: Hideshi
authors.initials: H
authors.lastname: Okada
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D002311:Cardiomyopathy, Dilated / Q000473:pathology; D006224:Cricetinae; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000473:pathology*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor