Molecular Mechanism of Aerobic Exercise Regulating YAP to Improve TAC-Induced Heart Failure

Statistical chart of mRNA expression analysis of natriuretic peptide A (NPPA) n=3-6; Figure 2 g. Statistical chart of mRNA expression analysis of natriuretic peptide B (NPPB). n=4-6. Compared with the TAC group, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Fig 3.

Aerobic exercise and Verteporfin intervention improved myocardial fibrosis and cardio-myocyte hypertrophy: Figure 3 a. Representative images of Masson staining of myocardial tissue (scale bars: 1 mm, 50 µm) ; Figure 3 b. Representative images of HE staining of myocardial tissue (scale bars: 1 mm, 50 µm), WGA staining (scale bar: 50 µm), and transmission electron microscopy (TEM, scale bar: 500 nm) ; Figure 3 c.

Statistical chart of the analysis results of the degree of cardiac fibrosis (CVF). n=3; Figure 3 d. Statistical analysis chart of the cross-sectional area of cardiomyocytes, unit: µm². n=6; Figure 3 e. Statistical chart of mRNA expression analysis of POSTN. n=4-5; Figure 3 f.

Statistical chart of mRNA expression analysis of type I collagen (Col1a1). n=3-4; Figure 3 g. Statistical chart of mRNA expression analysis of type III collagen (Col3a1). n=3-5. Compared with the TAC group. Fig 4.

Aerobic exercise and Verteporfin intervention increased the expression of YAP: Figure 4 a. Representative images of YAP-related protein expression. n=3 ; Figure 4 b. Statistical chart of YAP protein expression. n=4 ; Figure 4 c.

Statistical chart of p-YAP protein expression. n=3 ; Figure 4 d. Statistical chart of mRNA expression analysis of cysteine-rich protein 61 (YCR61) in myocardial tissue. n=4-5 ; Figure 4 e. Statistical chart of mRNA expression analysis of connective tissue growth factor (CTGF) in myocardial tissue. n=3-6 ; Figure 4 f.

Statistical chart of YAP fluorescence intensity in myocardial tissue. n=3 ; Figure 4 g. Representative images of YAP immunofluorescence results in myocardial tissue (scale bar: 50 µm). n=3. Compared with the TAC group, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Fig 5.

Aerobic exercise and Verteporfin intervention reduced myocardial and mitochondrial ul-trastructure pathological changes : Figure 5 a. Transmission electron microscopy (TEM, scale bars from top to bottom are 2 μm-4000x, 2 μm-10000x, 500 nm-30000x, 200 nm-50000x) ; Figure 5 b. Statistical chart of the proportion of mitochondrial damage ; Figure 5 c.

Statistical chart of mRNA expression analysis of mito-chondrial fusion protein (MFN2). n=5-6 ; Figure 5 d. Statistical chart of mRNA expression analysis of pro-apoptotic protein (BNIP3). n=4. Compared with the TAC group, *p < 0. 05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Fig 6.

Aerobic exercise and Verteporfin intervention reduced myocardial immune cell infiltra-tion : Figure 6 a. Representative transmission electron microscopy images of immune cells (scale bars:2µm-4000x,2µm-10000x,2µm-10000x); Figure 6 b. Representative images of YAP immunofluorescence results in myocardial tissue (scale bar: 50 µm) ; Figure 6 c.

Statistical chart of mRNA expression analysis of chemokine ligand 5 (CCL5). n=4-6 ; Figure 6 d. Statistical chart of mRNA expression analysis of C-C motif chemokine receptor 2 (CCR2). n=3-5 ; Figure 6 e. Statistical chart of mRNA expression analysis of C-X-C motif chemokine ligand 2 (CXCL2). n=3-5 ; Figure 6 f.

Statistical chart of mRNA expression analysis of G-protein coupled CXC chemokine receptor 2 (CXCR2) n=4-6. Compared with the TAC group, **p < 0.01, ***p < 0.001, ****p < 0.0001. Fig 7. Aerobic exercise and Verteporfin intervention reduced the level of myocardial inflamma-tion: Figure 7 a.

Representative images of the expression of M1 macrophage markers and inflamma-tion-related proteins. n=3 ; Figure 7 b. Statistical chart of iNOS protein expression. n=3 ; Figure 7 c. Statistical chart of ASC protein expression. n=3 ; Figure 7 d.

Statistical chart of IL-1β protein expression. n=3 ; Figure 7 e. Statistical chart of mRNA expression analysis of NLRP3. n=4-5 ; Figure 7 f. Statistical chart of mRNA expression analysis of IL – 6. n=4-7 ; Figure 7 g.

Statistical chart of mRNA expression analysis of IL-1β. n=6 ; Figure 7 h. Statis-tical chart of mRNA expression analysis of IL – 18. n=3-5. Compared with the TAC group, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Fig 8.

Aerobic exercise and Verteporfin intervention improved myocardial anti-inflammatory repair ability: Figure 8 a. Representative images of the expression of M2 macrophage markers and an-ti-inflammatory related proteins. n=3 ; Figure 8 b. Statistical chart of CD206 protein expression. n=3 ; Figure 8 c.

Statistical chart of IL-10 protein expression. n=3 ; Figure 8 d. Statistical chart of mRNA expression analysis of Arg – 1. n=4-6 ; Figure 8 e. Statistical chart of mRNA expression analysis of YM1. n=3-5 ; Figure 8 f.

Statistical chart of mRNA expression analysis of VEGFa. n=4-5. Compared with the TAC group, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Fig 9. Aerobic exercise regulation YAP improve TAC induced heart failure