Fig. 6.

SIRT5 deficiency causes hypertrophic cardiomyopathy. (A and B) Shortening fraction (A) and ejection fraction (B) were reduced in Sirt5 KO mice (n = 4 and 5 for Sirt5 WT and KO respectively, 8-week-old males). (C) Normalized heart weight of Sirt5 WT and KO male mice (n = 7 per genotype). (D–F) The shortening fraction (D), and ejection fraction (E) were significantly reduced whereas left ventricular mass to body mass (LVM/BM, F) was significantly increased in hearts of Sirt5 KO mice. (G) Representative M-mode images of echocardiography showing cardiac dysfunction in Sirt5 KO mice. (H and I) H&E staining of heart cross-sections (H) and quantification of cardiomyocytes cross-sectional areas (n = 100 per genotype, I) showing cardiac hypertrophy in the Sirt5 KO mice. The two black boxes in H indicate the localization of the images that are shown in larger magnification in Fig. S6J. (J) Masson’s trichrome stain in cross-sections of the heart showing increased fibrosis in Sirt5 KO hearts. (K) Evaluation of SMM, ANP, HSP90, and SIRT5 protein levels in Sirt5 WT and KO mouse hearts. Experiments in C–J were performed with hearts of 39-week-old male mice. All graphs shown as mean ± SEM, *P < 0.05, ****P < 0.0001.