title: Impaired autophagy contributes to adverse cardiac remodeling in acute myocardial infarction.
abstract: OBJECTIVE
  Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s), if any, during postinfarction cardiac remodeling.
  
  
  RESULTS
  Acute myocardial infarction (AMI) was induced by ligating left anterior descending (LAD) coronary artery. Autophagy was found to be induced sharply 12-24 hours after surgery by testing LC3 modification and Electron microscopy. P62 degradation in the infarct border zone was increased from day 0.5 to day 3, and however, decreased from day 5 until day 21 after LAD ligation. These results indicated that autophagy was induced in the acute phase of AMI, and however, impaired in the latter phase of AMI. To investigate the significance of the impaired autophagy in the latter phase of AMI, we treated the mice with Rapamycin (an autophagy enhancer, 2.0 mg/kg/day) or 3-methyladenine (3MA, an autophagy inhibitor, 15 mg/kg/day) one day after LAD ligation until the end of experiment. The results showed that Rapamycin attenuated, while 3MA exacerbated, postinfarction cardiac remodeling and dysfunction respectively. In addition, Rapamycin protected the H9C2 cells against oxygen glucose deprivation in vitro. Specifically, we found that Rapamycin attenuated NFκB activation after LAD ligation. And the inflammatory response in the acute stage of AMI was significantly restrained with Rapamycin treatment. In vitro, inhibition of NFκB restored autophagy in a negative reflex.
  
  
  CONCLUSIONS
  Sustained myocardial ischemia impairs cardiomyocyte autophagy, which is an essential mechanism that protects against adverse cardiac remodeling. Augmenting autophagy could be a therapeutic strategy for acute myocardial infarction.
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Lishan
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Fajiang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Xiaoen
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China; Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, and the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China; Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, and the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Luo
mesh_terms: D000208:Acute Disease; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D005947:Glucose; D010100:Oxygen; D020123:Sirolimus