RRC ID 11898
Author Kanamori H, Takemura G, Goto K, Maruyama R, Ono K, Nagao K, Tsujimoto A, Ogino A, Takeyama T, Kawaguchi T, Watanabe T, Kawasaki M, Fujiwara T, Fujiwara H, Seishima M, Minatoguchi S.
Title Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion.
Journal Am J Physiol Heart Circ Physiol
Abstract Ischemia is known to potently stimulate autophagy in the heart, which may contribute to cardiomyocyte survival. In vitro, transfection with small interfering RNAs targeting Atg5 or Lamp-2 (an autophagy-related gene necessary, respectively, for the initiation and digestion step of autophagy), which specifically inhibited autophagy, diminished survival among cultured cardiomyocytes subjected to anoxia and significantly reduced their ATP content, confirming an autophagy-mediated protective effect against anoxia. We next examined the dynamics of cardiomyocyte autophagy and the effects of manipulating autophagy during acute myocardial infarction in vivo. Myocardial infarction was induced by permanent ligation of the left coronary artery in green fluorescent protein-microtubule-associated protein 1 light chain 3 (GFP-LC3) transgenic mice in which GFP-LC3 aggregates to be visible in the cytoplasm when autophagy is activated. Autophagy was rapidly (within 30 min after coronary ligation) activated in cardiomyocytes, and autophagic activity was particularly strong in salvaged cardiomyocytes bordering the infarcted area. Treatment with bafilomycin A1, an autophagy inhibitor, significantly increased infarct size (31% expansion) 24 h postinfarction. Interestingly, acute infarct size was significantly reduced (23% reduction) in starved mice showing prominent autophagy before infarction. Treatment with bafilomycin A1 reduced postinfarction myocardial ATP content, whereas starvation increased myocardial levels of amino acids and ATP, and the combined effects of bafilomycin A1 and starvation on acute infarct size offset one another. The present findings suggest that autophagy is an innate and potent process that protects cardiomyocytes from ischemic death during acute myocardial infarction.
Volume 300(6)
Pages H2261-71
Published 2011-6-1
DOI 10.1152/ajpheart.01056.2010
PII ajpheart.01056.2010
PMID 21421825
MeSH Animals Autophagy / drug effects Autophagy / physiology* Autophagy-Related Protein 5 Cells, Cultured Coronary Occlusion / complications* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Lysosomal-Associated Membrane Protein 2 / antagonists & inhibitors Lysosomal-Associated Membrane Protein 2 / metabolism Macrolides / pharmacology Male Mice Mice, Inbred C57BL Mice, Transgenic Microtubule-Associated Proteins / antagonists & inhibitors Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Models, Animal Myocardial Infarction / etiology* Myocardial Infarction / metabolism Myocardial Infarction / physiopathology* Myocardial Ischemia / metabolism Myocardial Ischemia / physiopathology* Myocytes, Cardiac / drug effects Myocytes, Cardiac / metabolism Myocytes, Cardiac / pathology RNA, Small Interfering / pharmacology
IF 3.864
Times Cited 113
Mice RBRC00806