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Article Addendum

Autophagic Degeneration and Death of Cardiomyocytes in Heart Failure

Genzou Takemura, Shusaku Miyata, Yukinori Kawase, Hideshi Okada, Rumi Maruyama, and Hisayoshi Fujiwara

volume 2 | issue 3

July/August/September 2006
Pages: 212 - 214

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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 autophagic findings, an increase in cardiomyocyte size, and a reduction in myocardial fibrosis. G-CSF induced changes in molecular signaling included activation of Akt and 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. By contrast, neither cardiomyocyte apoptosis nor regeneration of cardiomyocytes from bone marrowderived cells was significant. It thus appears that autophagic death is an important contributor to cardiomyocyte loss in the cardiomyopathic hamster and that G-CSF exerts a beneficial effect, mainly via an antiautophagic mechanism.

Addendum to:
Autophagic Cardiomyocyte Death in Cardiomyopathic Hamsters and Its Prevention by Granulocyte Colony-Stimulating Factor
S. Miyata, G. Takemura, Y. Kawase, Y. Li, H. Okada, R. Maruyama, H. Ushikoshi, M. Esaki, H. Kanamori, L. Li, Y. Misao, A. Tezuka, T. Toyo-Oka, S. Minatoguchi, T. Fujiwara and H. Fujiwara
Am J Pathol 2006; 168:386-97



We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.