RRC ID 5359
著者 Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M, Nishida K, Hori M, Mizushima N, Otsu K.
タイトル The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.
ジャーナル Nat Med
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.
巻・号 13(5)
ページ 619-24
公開日 2007-5-1
DOI 10.1038/nm1574
PII nm1574
PMID 17450150
MeSH Animals Autophagy* Autophagy-Related Protein 5 Body Weight Cardiomegaly / genetics Cardiomegaly / pathology Echocardiography Heart / physiology* Humans Mice Mice, Transgenic Microtubule-Associated Proteins / genetics Muscle Cells / cytology Muscle Cells / pathology Muscle Cells / physiology* Tamoxifen / pharmacology
IF 36.13
引用数 978
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
実験動物マウス RBRC00806