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. 2019 Jul 17;8(15):e011012. doi: 10.1161/JAHA.118.011012

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© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Analysis of the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) dependent genes. A, Fifty‐one (male) and 68 (female) of the GR‐associated genes are related with abnormalities of the heart ventricle. Only 17 and 19 of the MR‐associated genes dysregulated in cardiomyocyte‐specific glucocorticoid receptor knockout (cardioGRKO hearts were identified within this category (lower panel). Atrial natriuretic peptide (Nppa), brain type natriuretic peptide (Nppb), and cyclooxygenase (Ptgs2) were identified among the common genes. Among the unique MR dependent genes was the vascular endothelial growth factor A (VegfA). Angiotensinogen (Agt) expression seems to be compromised only in male cardioGRKO hearts and its dysregulation is related to alterations in GR signaling. Dysregulation in Agt gene expression is associated with genes involved in cardiac hypertrophy. B, Visualization of the genes connected to Agt in male and female cardioGRKO (upper panel), and network of genes associated with VegfA. Alterations in VegA is associated with genes involved in hypertrophy and angiogenesis. Red depicts induced genes and green represents repressed genes. Orange lines (—) predict activation and blue lines predict inactivation. Yellow lines symbolize gene expression opposite to predicted effect, and gray lines represent that not prediction can be inferred based on the gene expression data. Nppa, Nppb, and Ptgs2 are marked with red asterisk (*). Agt is marked with a purple *, and VegA is marked with an orange *. CardioGRKO indicates cardiomyocyte‐specific glucocorticoid receptor knockout; CGRkO, cardiomyocyte‐specific glucocorticoid receptor knockout; GR, glucocorticoid receptor; MR, mineralocorticoid receptor.