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6 authors, including:
Genzou Takemura
Hideshi Okada
Asahi University
Gifu University
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ABSTRACT
Numerous cardiomyocytes were found to show autophagic vacuolar degeneration in
the UM-X7.1 hamster model of human dilated cardiomyopathy, and autophagy-related
proteinsi.e., ubiquitin, cathepsin D and Rab7were 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-, 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.
KEY WORDS
autophagy, cardiomyopathy, cytokines, heart failure,
remodeling
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Addendum to:
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Genzou Takemura
Shusaku Miyata
Yukinori Kawase
Hideshi Okada
Rumi Maruyama
Hisayoshi Fujiwara*
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Autophagy is the type 2 programmed cell death that occurs during tissue and organ
development in order to eliminate unnecessary cells,7-9 but it also has survival-oriented
functions, protecting cells from stresses such as starvation.8-10 Autophagic cell death is
actually a morphological term derived from electron microscopy observations and denotes
a form of cell death in which abundant autophagic vacuoles are present in the cytoplasm.
But this definition tells us nothing about the pathophysiological function of autophagy in
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Autophagy
Figure 1. Cardiomyocyte death pathways in heart failure. Three autophagy-related pathways are proposed. For details on the terms (oncotic and apoptosis
interruptus), please see references 13 and 14, respectively.
www.landesbioscience.com
Autophagy
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Autophagy