Fig. 4: Mice with disrupted propionyl-CoA handling develop cardiac contractile dysfunction.
a, Body weight, heart weight (HW):tibia length (TL) ratio and wet:dry lung weight ratio (n = 10, 14, 16 and 19 animals). *GEN denotes significant (P < 0.05) effect of genotype. Two-way ANOVA followed by multiple comparisons test. b, Cell dimensions and intracellular pH measured in cSNARF1-loaded myocytes. Hierarchical analyses from a total of 93–113 cells per genotype from 4–5 isolations. c, Cine MR imaging of 8-week mouse hearts showing rendered heart mass, LV end-diastolic (ED) end-systolic (SV) volumes, and LVED and LVES after normalising to body weight—that is, indexed (n = 8, 10, 10 and 9 animals). *GEN denotes significant (P < 0.05) effect of genotype. *GEN×SEX denotes significant (P < 0.05) interaction between sex and genotype (ordinary two-way ANOVA with Tukey’s multiple comparisons test). d, Echocardiography of female mice scanned at three timepoints (8 weeks, 14 weeks and 20 weeks) and their body weight. E/E′ and E′/A′ were measured from pulsed wave and tissue Doppler in apical four-chamber view; SV and cardiac output were measured in parasternal short-axis view (n = 4 and n = 4 animals, repeated-measures ANOVA). *GEN denotes significant (P < 0.05) effect of genotype. Mean ± s.e.m. e, Calcium signaling measured by fluorescence imaging of myocytes freshly isolated from 8-week-old amPA or amWT hearts. Protocol measured electrically evoked CaTs to obtain diastolic and systolic Ca2+ and CaT amplitude (amp). After a train of CaTs, a CaffT was produced to interrogate resting Ca2+, SR Ca2+ load and fractional release. Hierarchical analysis of 226–240 myocytes from n = 7, 7, 8 and 9 isolations. *P < 0.05. Mean ± s.e.m. BPM, beats per minute; BW, body weight; F, female; M, male; NS, not significant.
