Cardiac autophagy is a maladaptive response to hemodynamic stress
J. Clin. Invest. Hongxin Zhu, et al. 117:1782 doi:10.1172/JCI27523 [Go to this article.]

Figure 1
Cardiomyocyte autophagy triggered by short-term nutrient deprivation or pressure-overload hemodynamic stress. (A) Representative electron micrographs from the septa of 48-hour sTAB LVs (WT C57BL/6 mice) demonstrate the presence of double-membrane autophagosomes (arrows) and autolysosomes containing cellular material. These features are more prominent in sTAB ventricles compared with those of sham-operated controls. Scale bar: 120 nm. (B) Representative immunoblot for LC3 showing an increase in LC3-II abundance following sTAB as early as 24 hours after operations and persisting for at least 2 weeks. (C) Quantification of LC3-II/LC3-I levels demonstrates significant autophagic activity induced by pressure overload. *P < 0.05 versus Sham. (D) Representative immunoblots for LC3 in liver and kidney demonstrating that LC3-II abundance does not change in these tissues following sTAB. (E) Under baseline conditions, GFP-LC3 Tg fusion protein is diffusely distributed throughout the cardiomyocyte cytoplasm in α-MHC–GFP–LC3 mice. Following short-term (48 hours) starvation, GFP-LC3 aggregates as autophagosome-localized GFP dots. Representative images from basal septum are shown. Scale bar: 35 μm. (F) Following sham operation, GFP-LC3 Tg fusion protein is diffusely distributed throughout the cardiomyocyte cytoplasm in α-MHC–GFP–LC3 mice. Following imposition of pressure stress by sTAB (48 hours), GFP-LC3 aggregates as autophagosome-localized GFP dots. Representative images from basal septum are shown. Scale bar: 35 μm. (G) Quantification of GFP aggregates per microscopic field (14,479 μm²) demonstrates significant autophagic activity induced by starvation. For each group, at least 4 mice were studied. ^‡P < 0.01 versus fed. (H) Quantification of GFP aggregates per microscopic field (14,479 μm²) demonstrates significant autophagic activity induced by pressure overload. For each group, at least 4 mice were studied. ^†P < 0.01 versus sham. FW, free wall of LVs.