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.

journal_name

Autophagy

journal_title

Autophagy

authors

Takemura G,Miyata S,Kawase Y,Okada H,Maruyama R,Fujiwara H

doi

10.4161/auto.2608

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

212-4

issue

3

eissn

1554-8627

issn

1554-8635

pii

2608

journal_volume

2

pub_type

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