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The role of emerging autophagy in postinfarction cardiac remodeling.
MedLine Citation:
PMID:  21406597     Owner:  NLM     Status:  Publisher    
Aims Autophagy is activated in cardiomyocytes in ischemic heart disease, but dynamics and functional roles remain unclear after myocardial infarction. We observed dynamics of cardiomyocyte autophagy and examined its role during postinfarction cardiac remodeling. Methods and Results Myocardial infarction was induced in mice by ligating the left coronary artery. During both the subacute and chronic stages (1 and 3 weeks postinfarction, respectively), autophagy was found to be activated in surviving cardiomyocytes, as demonstrated by the upregulated expression of microtubule-associated protein-1 light chain 3-II (LC3-II), p62 and cathepsin D, and by electron microscopic findings. Activation of autophagy, specifically the digestion step, was prominent in cardiomyocytes 1 week postinfarction, especially in those bordering the infarct area, while the formation of autophagosomes was prominent 3 weeks postinfarction. Bafilomycin A1 (an autophagy inhibitor) significantly aggravated postinfarction cardiac dysfunction and remodeling. Cardiac hypertrophy was exacerbated in this group and was accompanied by augmented ventricular expression of atrial natriuretic peptide. In those hearts, autophagic findings (i.e., expression of LC3-II and the presence of autophagosomes) were diminished, and activation of AMP-activated protein kinase was enhanced. Treatment with rapamycin (an autophagy enhancer) brought about opposite outcomes, including mitigation of cardiac dysfunction and adverse remodeling. A combined treatment with bafilomycin A1 and rapamycin offset each effect on cardiomyocyte autophagy and cardiac remodeling in the postinfarction heart. Conclusions These findings suggest that cardiomyocyte autophagy is an innate mechanism that protects against progression of postinfarction cardiac remodeling, implying that augmenting autophagy could be a therapeutic strategy.
Hiromitsu Kanamori; Genzou Takemura; Kazuko Goto; Rumi Maruyama; Akiko Tsujimoto; Atsushi Ogino; Toshiaki Takeyama; Tomonori Kawaguchi; Takatomo Watanabe; Takako Fujiwara; Hisayoshi Fujiwara; Mitsuru Seishima; Shinya Minatoguchi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-15
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
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