Fig. 8: The α-MHC K1897R mutant partially abolishes the protective effect of NALA against Ang II-induced heart failure.

a Schematic for experimental intervention patterns. α-MHC WT mice were given control treatment or Ang II infusion. α-MHC K1897R KI mice were given control treatment/Ang II infusion/NALA infusion/combined Ang II and NALA infusion. b Relative content of myocardial tissue lactate in mice after the indicated treatment (n = 10 per group). c, d Representative WB and quantification of α-MHC K1897 Lactyl Lysine in myocardial tissues from mice after the indicated treatment. Tubulin was used as an internal reference (n = 3 per group). e, f Immunoprecipitation using anti-Titin antibody or control IgG (e), followed by detection of α-MHC. Quantification of the interaction of α-MHC with Titin (f). Tubulin was used as an internal reference (n = 3 per group). g Representative M-mode echocardiogram of mice after the indicated treatment. h Cardiac function was evaluated by EF (n = 10 per group). i Masson staining to detect myocardial fibrosis. j Quantification of the fibrotic area (n = 10 per group). k Representative heart sections stained with H&E (top) and WGA (bottom) to detect the presence of hypertrophy in cardiomyocytes. l Quantitation of relative cardiomyocyte cross-sectional area (n = 10 per group). m, n WB and quantification of fibrosis marker (α-SMA, Col-1) levels in myocardial tissues. Tubulin was used as an internal reference (n = 4 per group). o, p WB and quantification of cardiac injury indicator (cleaved-Caspase3 and cleaved-PARP1) levels in myocardial tissue, Tubulin was used as an internal reference (n = 4 per group). b, d, f, h, j, l, n, p Statistical significance was assessed by two-way ANOVA with Bonferroni multiple comparisons test (P values adjusted for 10 comparisons; ns no significance; *P < 0.05; **P < 0.01; ***P < 0.001).