Fig. 1: BMAL1 is a key transcription factor in circadian variations of myocardial injury.
From: BMAL1–HIF2A heterodimer modulates circadian variations of myocardial injury
a–d, RNA-seq analysis of the AAR from C57BL/6J mice after 2 h reperfusion at ZT8 or ZT20, n = 3 mice per timepoint. a, Expression z scores. b, The fold change (FC) in expression. c, Analysis of circadian expression of DEGs using RT–qPCR. d, The top ten enriched biological process GO terms. FDR, false-discovery rate. e–i, RNA-seq analysis of post-clamping LV biopsies from patients who had aortic valve replacement (AVR) surgery in the morning (AM; n = 56) or afternoon (PM; n = 17). e, The study design. f, Clustered Pearson’s correlations. CRI, chronic renal insufficiency; sCr, serum creatinine. g, The fold change in expression after clamping (morning versus afternoon). h, Enriched GO terms. i, Normalized read counts for DEGs. The box plots show the median (centre line), interquartile range (box limits), and the minimum to maximum values (whiskers). j, The experimental setup for cardiac injury and function assessment in Bmal1loxP/loxP myosin-Cre+ and myosin-Cre+ mice subjected to IRI at ZT8 or ZT20. I, ischaemia; R, reperfusion. k, Heart slices were stained with Evan’s blue and 2,3,5-triphenyltetrazolium chloride (TTC) after 2 h reperfusion; the infarct area (green) and AAR (blue) are shown. Scale bar, 1 mm. l, The AAR as the percentage of the LV. m, The infarct size as the percentage of the AAR. n = 7 mice per group per timepoint. n, Serum troponin I levels. n = 7 (Bmal1loxP/loxP myosin-Cre+) and n = 8 (myosin-Cre+) mice per timepoint. o–q, Cardiac function on day 14 after MI by STE. o, The EF, FS and GLS. p, 3D and six-segment longitudinal strain imaging with annotations for reduced contractility (stars), dyskinesis (triangles) and dyssynchrony (circles). Dark blue, anterior base; yellow, anterior mid; magenta, anterior apex; cyan, posterior apex; light pink, posterior mid; green, posterior base. q, The intraventricular delay. For o and q, n = 7 (Bmal1loxP/loxP myosin-Cre+) and n = 9 (myosin-Cre+) mice per timepoint. All samples are biologically independent. For c,l–o and q, data are mean ± s.e.m. Statistical analysis was performed using Wald tests (b and g), two-sided Fisher’s exact tests (d and h) and two-way analysis of variance (ANOVA; l–o and q). The diagram in j was created using BioRender.
