Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion.

摘要: Ischemia is known to potently stimulate autophagy in the heart, which may contribute cardiomyocyte survival. In vitro, transfection with small interfering RNAs targeting Atg5 or Lamp-2 (an autophagy-related gene necessary, respectively, for initiation and digestion step of autophagy), specifically inhibited autophagy, diminished survival among cultured cardiomyocytes subjected anoxia significantly reduced their ATP content, confirming an autophagy-mediated protective effect against anoxia. We next examined dynamics effects manipulating during acute myocardial infarction vivo. Myocardial was induced by permanent ligation left coronary artery green fluorescent protein-microtubule-associated protein 1 light chain 3 (GFP-LC3) transgenic mice GFP-LC3 aggregates be visible cytoplasm when activated. Autophagy rapidly (within 30 min after ligation) activated cardiomyocytes, autophagic activity particularly strong salvaged bordering infarcted area. Treatment bafilomycin A1, inhibitor, increased infarct size (31% expansion) 24 h postinfarction. Interestingly, (23% reduction) starved showing prominent before infarction. A1 postinfarction whereas starvation levels amino acids ATP, combined on offset one another. The present findings suggest that innate potent process protects from ischemic death