Autophagy in myocardium of murine hearts subjected to ischemia followed by reperfusion

Histochem Cell Biol. 2010 Nov;134(5):519-26. doi: 10.1007/s00418-010-0748-0. Epub 2010 Oct 8.

Abstract

Autophagy in myocardium has been thought to be cardioprotective, but its extent after transient or prolonged myocardial ischemia remains unclear. Accordingly, we characterized its magnitude in myocardium of murine hearts subjected to ischemia with or without reperfusion. Ten-week-old transgenic GFP-LC3 mice and C57Bl6 mice were subjected to coronary ligation for 1 or 4 h followed by 24 h of reperfusion (1HTL, 4HTL) or to 24 h of persistent ligation (24HPL). Their hearts were analyzed by fluorescence microscopy, electron microscopy, and by Western blotting. Fluorescent GFP-LC3 dots indicative of autophagy were absent in infarct zones and reduced markedly in the peri-infarct zones compared with dots in sham controls (p ≤ 0.05). The LC3-II/LC3-I ratio indicative of autophagy did not increase in LV homogenates from hearts following ischemia. Phosphorylation of ribosomal protein S6 increased in LV homogenates in hearts from mice subjected to 4HTL and 24HPL (p ≤ 0.05). Virtually no autophagic cells recognizable by electron microscopy were evident in infarct or peri-infarct zones. Autophagy is virtually absent within 24 h in the center of zones of infarction and is decreased significantly in the peri-infarct zones compared with that in normal hearts.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Blotting, Western
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Myocardium / ultrastructure
  • Phosphorylation
  • Ribosomal Protein S6 / metabolism

Substances

  • Ribosomal Protein S6