Impact of ovary-intact menopause in a mouse model of heart failure with preserved ejection fraction

Figures

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  Figure 1.. Study design and confirmation of follicle depletion following chemically induced accelerated ovarian failure (AOF). A: schematic of study design. B: representative hematoxylin-eosin (H&E)-stained midovarian sections from control and AOF mice. HFpEF, heart failure with preserved ejection fraction; VCD, vinylcyclohexene dioxide.

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  Figure 2.. Conventional echocardiography results from mice at 15 wk. A: representative M-mode images acquired from a midventricular short-axis view. B: left ventricle ejection fraction (LVEF) percentage. C: fractional shortening (FS). D: left ventricle anterior wall thickness at late diastole (LVAW;d, in mm). E: left ventricle posterior wall thickness at late diastole (LVPW;d, in mm). F: relative wall thickness (RWT). G: representative tissue and pulsed-wave Doppler recordings acquired from the septal mitral annulus and mitral orifice, respectively. H: mitral valve (MV) ratio of the early diastolic inflow wave to the mitral annulus tissue movement (E/e′). I: myocardial performance index (MPI). Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 6–14 animals/group; *P < 0.05, **P < 0.01). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 3.. Speckle-tracking stain echocardiography results from mice at 16 wk. A: cardiac output (CO). B: global longitudinal strain (GLS) percentage. C: peak longitudinal systolic strain rate (LSR;s). D: peak radial systolic strain rate (RSR;s). E: peak longitudinal diastolic strain rate (LSR;d). F: peak radial diastolic strain rate (RSR;d). Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 6–14 animals/group; *P < 0.05, **P < 0.01, ***P < 0.001). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 4.. Invasive hemodynamic measurements acquired from the aorta and left ventricle. A: systolic blood pressure (SBP). B: diastolic blood pressure (DBP). C: pulse pressure (PP). D: left ventricle pressure decay constant tau (logistic model). E: maximum left ventricle pressure derivative with respect to time (dP/dtmax). F: minimum left ventricle pressure derivative with respect to time (dP/dtmin). Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 4–6 animals/group; *P < 0.05, ***P < 0.001). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 5.. Ex vivo assessment of cardiac and myocyte hypertrophy. A: representative images of wheat germ agglutinin (WGA)-stained midventricular sections. B: heart weight-to-tibia length ratio (HW/TL). C: myocyte cross-sectional area. Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 6–12 animals/group; *P < 0.05, **P < 0.01, ***P < 0.001). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 6.. Assessment of capillary density via von Willebrand factor (vWBF) immunostaining. A: representative images of midventricular sections stained for vWBF with DAPI counterstaining. B: density of vWF puncta. Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 3 or 4 animals/group). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 7.. Evaluation of infiltrating leukocytes in the myocardium via immunostaining of midventricular section. A: density of CD45+ puncta. B: density of CD68+ puncta. Data are presented as means ± 95% confidence interval with individual replicates plotted as points (N = 5 animals/group; *P < 0.05, **P < 0.01, ***P < 0.001). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 8.. Relative levels of select circulating hormones measured on tandem liquid chromatography-mass spectrometry. Fold changes (FCs) for each hormone are given relative to the mean value for the ovary-intact control group. A: aldosterone fold change. B: corticosterone fold change. C: angiotensin II fold change. Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 5 animals/group; *P < 0.05, **P < 0.01). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 9.. Conventional echocardiography results from middle-aged “old” female mice at 15 wk from study inception. A: left ventricle ejection fraction (LVEF) percentage. B: left ventricle anterior wall thickness at late diastole (LVAW;d, in mm). C: left ventricle posterior wall thickness at late diastole (LVPW;d, in mm). D: relative wall thickness (RWT). E: mitral valve (MV) ratio of the early diastolic inflow wave to the mitral annulus tissue movement (E/e′). F: myocardial performance index (MPI). Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 2–5 animals/group). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 10.. Speckle-tracking stain echocardiography results from middle-aged “old” female mice at 15 wk from study inception. A: cardiac output (CO). B: global longitudinal strain (GLS) percentage. C: peak longitudinal systolic strain rate (LSR;s). D: peak radial systolic strain rate (RSR;s). E: peak longitudinal diastolic strain rate (LSR;d). F: peak radial diastolic strain rate (RSR;d). Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 2–5 animals/group). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.

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  Figure 11.. Invasive hemodynamic measurements acquired from the aorta and left ventricle of middle-aged “old” female mice. A: systolic blood pressure (SBP). B: diastolic blood pressure (DBP). C: pulse pressure (PP). D: left ventricle pressure decay constant tau (logistic model). E: maximum left ventricle pressure derivative with respect to time (dP/dtmax). F: minimum left ventricle pressure derivative with respect to time (dP/dtmin). Data are presented as means ± 95% confidence intervals with individual replicates plotted as points (N = 2–5 animals/group; *P < 0.05, ***P < 0.001). AOF, accelerated ovarian failure; HFpEF, heart failure with preserved ejection fraction.