Fig. 8: Overexpression of PERK mediates cardiac atrophy.

a Schematic diagram depicting the experimental protocol. Either 1E11 genomic copies of adeno-associated virus 9 (AAV9)-PERK or AAV9-luciferase (Lucif.) control were injected into the mediastinum of 7-day-old WT mouse pups. Hearts were harvested at 8 weeks of age for further analysis. b Low magnification of whole mount cardiac histological images from mice injected with AAV9-PERK or AAV9-Lucif. control stained with Masson’s trichrome at 8 weeks of age. Scale bar is 2 mm. c Representative western blots for PERK, ATF4, LC3b, and p62 from cardiac protein extracts of 8-week-old mice injected with either AAV9-Lucif. or AAV9-PERK. Gapdh serves as a loading control. d Representative western blot for ubiquitin-conjugated proteins (Ubiq.) and Gapdh as loading control on cardiac protein extracts of 8-week-old mice injected with either AAV9-Lucif. or AAV9-PERK. e HW/BW ratio (*P = 0.0051 vs AAV9-Lucif.) and f FS% at 8 weeks of age in the 2 indicated groups of mice. *P = 0.0060 vs AAV9-Lucif. g Representative immunohistochemistry for PERK (green), nuclei with DAPI (blue) and WGA (purple)-stained membranes from heart sections of AAV9-PERK or AAV9-Lucif. injected mice killed at 8 weeks of age. Scale bars are 100 μm. h Quantitative analysis of AAV9-Lucif. versus or AAV9-PERK positive (Pos.) and negative (Neg.) cross sectional area (CSA) determined by WGA staining of cardiac histological sections. *P = 0.0087 vs AAV9-Lucif. and *P = 0.0050 vs AAV9-PERK Neg. The number of biologically independent animals analyzed are indicated on the graphs. Statistical analysis was performed using a two-tailed Student’s t-test in panels “e, f”, and one-way ANOVA and Tukey multiple comparisons test in panel “h”. All error bars are ±standard error of the mean. Source data are provided as a Source Data File.