Reconstituted HDL (Milano) Treatment Efficaciously Reverses Heart Failure with Preserved Ejection Fraction in Mice

Figures

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  Figure 1. Schematic representation of the study design.

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  Figure 2. Body weight (A), glucose level (B), insulin (C), heart weight (D), tibia length (E), heart weight/tibia length (F), left ventricular weight (G), right ventricular weight (H), atrial weight (I), and lung weight (J) in C57BL/6 standard chow (SC) diet mice and in C57BL/6 coconut oil (CC) diet mice. CC diet was initiated at 12 weeks of age. Quantifications were performed at 38 weeks, 26 weeks after the start of the diet. SC diet mice and CC diet mice are indicated by open bars and closed bars, respectively. All data represent means ± SEM (n = 15).

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  Figure 3. Quantification of histological and immunohistochemical parameters in the myocardium of C57BL/6 SC diet mice and C57BL/6 CC diet mice. Bar graphs showing the cardiomyocyte cross-sectional area (A), cardiomyocyte density (B), capillary density (C), relative vascularity (D), interstitial fibrosis (E), and perivascular fibrosis (F) in SC diet mice (n = 21) and CC diet mice (n = 30) at 38 weeks, 26 weeks after the start of diet. SC diet mice and CC diet mice are indicated by open bars and closed bars, respectively. All data represent means ± SEM.

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  Figure 4. Body weight (A), glucose level (B), insulin (C), heart weight (D), tibia length (E), heart weight/tibia length (F), left ventricular weight (G), right ventricular weight (H), atrial weight (I), and lung weight (J) in C57BL/6 SC diet mice and in C57BL/6 CC diet mice. CC diet was initiated at 12 weeks of age. Quantifications were performed at 38 weeks (reference mice) or at 40 weeks (buffer mice and MDCO-216 mice) on SC diet or CC diet. SC diet mice and CC diet mice are indicated by open bars and closed bars, respectively. All data represent means ± SEM (n = 15).

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  Figure 5. Quantification of histological and immunohistochemical parameters in the myocardium of C57BL/6 SC diet mice and C57BL/6 CC diet mice. Bar graphs showing the cardiomyocyte cross-sectional area (A), cardiomyocyte density (B), capillary density (C), relative vascularity (D), interstitial fibrosis(E), and perivascular fibrosis (F) in reference SC diet mice (n = 21), buffer SC diet mice (n = 12), MDCO-216 SC diet mice (n = 12), reference CC diet mice (n = 30), buffer CC diet mice (n = 14), and MDCO-216 CC diet mice (n = 17) at 38 weeks (reference mice) and at 40 weeks (buffer mice and MDCO-216 mice). The CC diet was initiated at 12 weeks of age. SC diet mice and CC diet mice are indicated by open bars and closed bars, respectively. All data represent means ± SEM.

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  Figure 6. Representative Sirius-red stained cross-sections of reference, buffer, and MDCO-216 SC diet and CC diet mice. Scale bar represents 1 mm.

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  Figure 7. Immunohistochemical and histochemical analysis of the myocardium of reference, buffer, and MDCO-216 SC diet and CC diet mice. Representative photomicrographs show laminin-stained cardiomyocytes, CD31-positive capillaries, and Sirius-red-stained collagen. Scale bar represents 50 µm.

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  Figure 8. Quantification of proteins in the myocardium by western blot. Bar graphs illustrating ACC (A), p-ACC (B), TGF-β1 (C), and osteopontin (D) protein levels quantified by western blot in the myocardium. SC diet mice and CC diet mice are indicated by open bars and closed bars, respectively. Representative images of western blots are shown in panel E. All protein levels were normalized to the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein level. All data represent means ± SEM (n = 6).

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  Figure 9. Lactate pre-exercise (A), distance covered (B), and lactate post-exercise (C) in C57BL/6 SC diet mice and in C57BL/6 CC diet mice. SC diet mice and CC diet mice are indicated by open bars and closed bars, respectively. All data represent means ± SEM (n = 15).