Fig. 3: Acly deletion in cardiac activated myofibroblasts preserves cardiac function and reduces interstitial fibrosis.

a, Tamoxifen-inducible, Cre-recombinase-mediated gene knockout of Acly and expression of R26-tdT in activated fibroblasts. b, Mice subjected to TAC at 0 week and started on tamoxifen chow to induce Cre-recombinase expression in activated CFs. Echocardiograms (Echo) performed every 4 weeks are indicated by arrows. Take-downs were performed at 8 weeks for interstitial fibrosis and gravimetrics. c, Western blot of ACLY knockout in Acly^fl/fl, Postn^iCre, R26-tdT CFs. d, Peak aortic pressure gradients from Postn^iCre, R26-tdT mice and Acly^fl/fl, Postn^iCre, R26-tdT mice that underwent TAC. Unpaired two-sided t-test. Postn^iCre, R26-tdT + TAC = 9 mice; Acly^fl/fl, Postn^iCre, R26-tdT + TAC = 8 mice. e, Echocardiographic data of mice followed 8 weeks after TAC. Long-axis, B-mode images. EF, ejection fraction; LVESV, LV end-systolic volume; LVEDV, LV end-diastolic volume. Two-way ANOVA with Tukey HSD. Comparisons between Postn^iCre, R26-tdT mice and Acly^fl/fl, Postn^iCre, R26-tdT mice at the same timepoint. Comparisons between different timepoints of the same genotype. Postn^iCre, R26-tdT + TAC = 10 mice at 0 week and 9 mice at 4 weeks and 8 weeks; Acly^fl/fl, Postn^iCre, R26-tdT + TAC = 10 mice at 0 week and 8 mice at 4 weeks and 8 weeks. f, B-mode speckle tracking calculations of LV strain rates at baseline (Base) and 8 weeks after TAC. Two-way ANOVA with Tukey HSD. Postn^iCre, R26-tdT + TAC = 10 mice at baseline and 9 mice at 8 weeks; Acly^fl/fl, Postn^iCre, R26-tdT + TAC = 10 mice at 0 week and 8 mice at 8 weeks. g, Picrosirius red staining of matrix protein in 10 μm LV sections. Scale bars, 200 μm. h, Percentage of the picrosirius red (PSR) stain over the total area. Outliers were identified by Grubbs test with an alpha of 0.05 and indicated with ‘×’ in the graph. Two-way ANOVA with Tukey HSD. i, Gravimetric data from mice at 8 weeks after TAC. HW, heart weight; TL, tibia length. Two-way ANOVA with Tukey HSD. For h and i, Postn^iCre, R26-tdT + sham = 7 mice; Acly^fl/fl, Postn^iCre, R26-tdT + sham = 5 mice; Postn^iCre, R26-tdT + TAC = 8 mice; and Acly^fl/fl, Postn^iCre, R26-tdT + TAC = 9 mice. All data are depicted as mean ± s.e.m. Full-length western blots are available as source data.

Source data