Table 1.
Body condition criteria.
Table 2.
Pilot study design.
Table 3.
Study design–Cardiac assessments in G3Stg/GlaKO mice.
Table 4.
Study design–Cardiac assessments in GlaKO mice.
Fig 1.
Representative echocardiography images: B-Mode and M-Mode in a G3Stg/GlaKO mouse and an age-matched WT:WT mouse.
Abbreviations: AO = Thoracic aorta, LV = Left ventricle, LVAW = Left ventricular anterior wall, LVID = Left ventricular internal diameter, LVPW = Left ventricular posterior wall.
Fig 2.
Characterization of cardiac function, left ventricular (LV) wall thickness, heart rate (HR), LV mass and organ weight in HEMI: CAR and age-matched WT: WT.
For values and stats, see S4 Table in S1 Appendix. * p ≤0.05, ** p ≤0.01, *** p ≤0.001. The p values are Bonferroni corrected. Number of animals per group = 25.
Fig 3.
Longitudinal (5–13 months of age) assessments of LV mass, end-diastolic volume, and LV internal diameter indicate cardiomegaly and volume overload in GlaKO and age-matched WT mice.
Number of animals per group = 20–21. Statistical analysis was performed using longitudinal mixed modeling and shown in S5 Table in S1 Appendix. * p ≤0.05, ** p ≤0.01, *** p ≤0.001. P values were adjusted using the Tukey method to control for Family Wise Error Rate (FWER).
Fig 4.
Characterization of cardiac function, LV wall thickness, heart rate, LV mass and organ weight in non-symptomatic GlaKO Fabry mice and age-matched WT controls at 13 months of age.
Number of animals per group = 20–21. A. Cardiac function: Ejection fraction was lower in GlaKO mice (8% decrease) with no change in fractional shortening and cardiac output. Increase in stroke volume (16% increase), and significant increases in end-systolic volume (volume systole) and end-diastolic volume (volume diastole) by up to 28%, were observed in GlaKO mice. B. Cardiac wall thickness (LV anterior and posterior walls) of GlaKO mice were the same when compared to age-matched WT mice, but their LV internal diameter was significantly wider (up to 8% increase). C. LV mass of GlaKO mice was greater than WT (12% increase). Heart rate was significantly lower in GlaKO mice (9% decrease). D. Terminal organ collection. 13 months old mice show trend of increase in heart weight and in heart weight to brain weight Ratio (17% and 18% increase, respectively). Statistical analysis was performed using longitudinal mixed modeling across all ages, extracted for month 13, and shown in S6 Table in S1 Appendix. * p ≤0.05, ** p ≤0.01, *** p ≤0.001. Tukey method of p value correction was used to control for family wise error rate.
Fig 5.
Compromised GLS and radial strain in GlaKO mice.
A. Single frame from echocardiography scan (long axis), indicating endocardium and epicardium contours. B. example of a cardiac contraction over time during one heartbeat. C, D. peak amplitude and area under the curve (AUC) of global longitudinal strain (GLS) of endocardium. E, F. peak amplitude and AUC of GLS of epicardium. G, H. peak amplitude and AUC of radial strain. For stats, see S7 Table in S1 Appendix. * p≤0.05, ** p≤0.01, *** p≤0.001. p Values are Bonferroni corrected for multiple comparisons.
Fig 6.
Translatability of strain measurements in mice.