title: The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.
abstract: Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a beneficial or detrimental role in the heart. Here, we report that the cardiac-specific loss of autophagy causes cardiomyopathy in mice. In adult mice, temporally controlled cardiac-specific deficiency of Atg5 (autophagy-related 5), a protein required for autophagy, led to cardiac hypertrophy, left ventricular dilatation and contractile dysfunction, accompanied by increased levels of ubiquitination. Furthermore, Atg5-deficient hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation. On the other hand, cardiac-specific deficiency of Atg5 early in cardiogenesis showed no such cardiac phenotypes under baseline conditions, but developed cardiac dysfunction and left ventricular dilatation one week after treatment with pressure overload. These results indicate that constitutive autophagy in the heart under baseline conditions is a homeostatic mechanism for maintaining cardiomyocyte size and global cardiac structure and function, and that upregulation of autophagy in failing hearts is an adaptive response for protecting cells from hemodynamic stress.
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka 565-0871, Japan.
authors: Atsuko
authors: A
authors: Nakai
authors: Osamu
authors: O
authors: Yamaguchi
authors: Toshihiro
authors: T
authors: Takeda
authors: Yoshiharu
authors: Y
authors: Higuchi
authors: Shungo
authors: S
authors: Hikoso
authors: Masayuki
authors: M
authors: Taniike
authors: Shigemiki
authors: S
authors: Omiya
authors: Isamu
authors: I
authors: Mizote
authors: Yasushi
authors: Y
authors: Matsumura
authors: Michio
authors: M
authors: Asahi
authors: Kazuhiko
authors: K
authors: Nishida
authors: Masatsugu
authors: M
authors: Hori
authors: Noboru
authors: N
authors: Mizushima
authors: Kinya
authors: K
authors: Otsu
mesh_terms: D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D001835:Body Weight; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology; D004452:Echocardiography; D006321:Heart / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics; D032342:Muscle Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D013629:Tamoxifen