Cardiomyocyte glucocorticoid receptor and transcriptional rhythms in the heart

Ventricular arrhythmias demonstrate a prominent diurnal rhythm, commonly presenting in the morning on waking. Transcriptional rhythms in cardiac ion channels contribute to this phenomenon but the underlying mechanisms are incompletely understood. We have evidence in mice suggesting the glucocorticoid receptor (GR), the transcriptional effector of glucocorticoids, regulates ion channels previously implicated in the diurnal rhythm in cardiomyocyte excitability and ventricular arrhythmia susceptibility. To determine if the GR is a direct regulator of the transcriptional rhythms in the heart, RNA-seq was performed on RNA isolated from the left ventricular (LV) free wall of cardiomyocyte-specific GR knockout mice (cardioGRKO) and their littermate control mice (GRflox) at ZT0 (start of lights on) and ZT12 (start of lights off) time points. Mice with conditional knockout of GR in cardiomyocytes (cardioGRKO) have been previously described (Sci Signal. 2019 Apr 16;12(577):eaau9685. doi: 10.1126/scisignal.aau9685). Hearts were removed from adult male cardioGRKO mice and their littermate control mice (GRflox) at ZT0 (start of lights on) and ZT12 (start of lights off) time points. The left ventricular (LV) free wall was dissected from the heart. Total RNA was isolated from the LV free wall using Qiagen RNeasy Mini kit. A TruSeq RNA kit (Illumina, San Diego, CA) was utilized to prepare the poly(A)-enriched RNA-seq libraries that were sequenced on the Illumina NovaSeq 6000 in a 75-base paired-end mode according to the manufacturer’s protocol.