Fig 2: Histological analysis of wild‐type and Itga7 −/− cardiac muscle.Transversal view of immunostaining for integrin α7 (green) (A, C, D, F, H, and I) and connexin‐43 (red) (A, B, C, E, F, G, H, and J) in wild‐type (A‐E) and Itga7 −/− (F through J) cardiac muscle. Connexin‐43 localization is restricted to the intercalated discs in wild‐type cardiomyocytes (A, B, C, and E), whereas connexin‐43 is redistributed to the lateral membrane of the Itga7 −/− (F, G, H, and J) cardiomyocytes. Sirius Red staining for wild‐type (K and K′) and Itga7 −/− (L and L') cardiac muscle reveals no significant changes in fibrosis levels in the absence of integrin α7. Yellow arrows indicate positive staining for integrin α7 (D) and connexin‐43 (E and J). The merge images include 4'6‐diamidino‐2‐phenylindole (blue), integrin α7 (green), and connexin‐43 (red). Cx43 indicates connexin‐43; Itga7 −/−, integrin α7 knockout; and WT, wild‐type. Representative images of n=3 for each genotype. Scale bar: 25 μm.

Fig 3: Echocardiography analysis in wild‐type and Itga7 −/− mice.Representative echocardiograms (M‐mode view) of 10‐month‐old wild‐type (n=12) (A) and Itga7 −/− mice (n=12) (B). Echocardiographic measurements show reduced ejection fraction (D), fractional shortening (E), cardiac output (F), and stroke volume (G) in Itga7 −/− mice suggesting systolic dysfunction. No significant differences were found in left ventricular (LV) mass/body weight ratio (C), LV systolic volume (H), LV diastolic volume (I), LV posterior wall thickness at systole (J), LV internal diameter at systole (L), LV internal diameter at diastole (M), and LV anterior wall thickness at diastole (O). Itga7 −/− mice presented a significant increase of about 14% in LV posterior wall thickness at diastole (K) and a decrease of about 20% in LV anterior wall thickness at systole (N). Student t‐test analysis represented by statistical significance of mean ± SEM.*P<0.05, **P<0.01. d indicates diastole; Itga7 −/−, integrin α7 knockout; LV, left ventricle; LVAW, left ventricular anterior wall; LVID, left ventricular internal diameter; LVPW, left ventricular posterior wall; and WT, wild‐type.

Fig 4: Electrocardiography analysis in wild‐type and Itga7 −/− mice.Representative traces are shown from a lead II ECG from 10‐month‐old wild‐type (n=10) (A) and Itga7 −/− mice (n=8) (B). Quantitative evaluation reveals prolonged P duration (E) and PR interval (F) suggesting alterations in conduction through the atrioventricular node, and prolonged QRS interval (G) and QT interval (H) in Itga7 −/− mice indicating ventricular conduction delay. No significant difference was found in heart rate (C), RR interval (D), P amplitude (I), Q amplitude (J), S amplitude (L), and T amplitude (M). In the absence of integrin α7, R amplitude (K) is significantly decreased. Student t‐test analysis represented by statistical significance of mean±SEM.*P<0.05, **P<0.01. Itga7−/ − , indicates integrin α7 knockout; and WT, wild‐type.

Fig 5: Reduced ITGA7 expression protects breast cancer cells from chemotherapy.MCF7 cells were transfected with siRNA targeted against ITGA7 (si ITGA7) or with nontargeting siRNA control (con). Cells were treated with doses of epirubicin 24 h after transfection, for a further 48 h (left) or 72 h (right) before relative cell survival was determined using MTT assays. Error bars represent SEM of three fully independent experiments. * Indicates significant differences at specific doses (p < 0.05; Mann–Whitney test). ns denotes not significant.