Cell Type-Specific Roles for BRD4 in Heart Failure

This review synthesizes recent literature on cell type-specific roles for BRD4 in cardiac homeostasis and disease, emphasizing functions for this chromatin 'reader protein' in mediating pathologic gene signatures in heart failure.

Paradoxically, although knockout of BRD4 in cardiomyocytes is catastrophic, pharmacological inhibition of BRD4 blocks pathological cardiac remodeling via salutary effects in cardiomyocytes as well as in cardiac fibroblasts and macrophages. Mechanistically, dynamic targeting of BRD4 to gene enhancers and promoters governs stress-induced pathogenic transcriptional programs across myocyte and non-myocyte cell populations in the heart. Recent findings support roles for BRD4 in promoting pro-hypertrophic, pro-inflammatory, and pro-fibrotic gene expression via cell autonomous and non-autonomous actions in multiple cardiac cell types. Advancements in understanding the mechanisms by which BRD4 controls pathological gene expression in the heart should facilitate efforts to develop effective agents to target this epigenetic reader for the treatment of heart failure.