Healthy longevity-associated protein improves cardiac function in murine models of cardiomyopathy with preserved ejection fraction

Figures

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  Fig. 1. Primary endpoints of the study in older mice. A Experimental protocol. B Body weight at baseline and the end of the follow-up. C Representative echocardiography traces. D–H Echocardiography data: left ventricular mass (D), left ventricular volume at the end of diastole (E) and systole (F), left ventricular ejection fraction (G), and left ventricular fractional shortening (H). Each point represents a single mouse, with a line connecting the baseline and final measurements. The mean values and standard deviations are reported in Supplementary Table 2

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  Fig. 2. Effect of treatment on the myocardial expression of BPIFB4. A Representative images with inserts. B Bar graphs with individual values

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  Fig. 3. Histological endpoints of the study in older mice. A Representative images illustrating the abundance of capillaries and arterioles. The inserts show specific staining. B Bar graphs with individual values of capillary and arteriole density in the whole left ventricular wall and single regions of the heart. C, D Quantification of vessels covered by PDGFRβ PCs. Representative images with inserts (C) and bar graphs with individual values for capillary and arteriole coverage in the whole left ventricular wall and single regions of the heart (D). E, F Quantification of fibrosis via Azan-Mallory staining. Representative images (E) and bar graphs with individual values of perivascular and interstitial fibrosis (F)

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  Fig. 4. Effect of treatment on markers of viability and senescence. A, B TUNEL staining for visualization and quantification of apoptotic cells. Representative images with inserts (A) and bar graphs with individual values (B). C, D Staining with P16ink4A for visualization and quantification of senescent cells. Representative images with inserts (C) and bar graphs with individual values (D) are shown. E, F Staining with SA-β-Gal for visualization and quantification of senescent cells. Representative images with inserts E and bar graphs with individual values F are shown

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  Fig. 5. Main endpoints of the study in male and female diabetic mice. A Experimental protocol. B Body weight at baseline and at the end of the follow-up. C Urinary glucose levels. D-H) Echocardiography data: left ventricular mass (D), left ventricular volume at the end of diastole (E) and systole (F), left ventricular ejection fraction (G), and left ventricular fractional shortening (H). Each point represents a single mouse, with a line connecting the baseline and final measurements. The mean values and standard deviations are reported in Supplementary Table 3

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  Fig. 6. Vascular endpoints of the study in diabetic mice. A Representative images illustrating the abundance of capillaries and arterioles. B Graphs with individual values of capillary density (B) and arteriole density (B). C, D P16inkA + senescent cells (illustrative images (C) and graphs (D))