Targeting bromodomain and extraterminal proteins in cardiovascular disease: Pathological mechanisms and therapeutic applications

Bromodomain and extraterminal proteins have emerged as key epigenetic regulators that coordinate transcriptional programs fundamental to cardiovascular physiology and disease. Although bromodomain and extraterminal protein inhibitors exert multiple cardiovascular effects, they cannot fully explain clinical heterogeneity in outcomes and responses, highlighting the need to clarify the context- and disease-specific roles of individual bromodomain and extraterminal protein family members. This narrative review delineates the distinct molecular roles of bromodomain-containing protein 2, bromodomain-containing protein 3, bromodomain-containing protein 4, and bromodomain testis, summarizing their domain architecture and epigenetic regulatory functions. We then synthesize current evidence linking bromodomain and extraterminal protein activity to cardiovascular disease pathogenesis, emphasizing their contributions to major pathological processes, including inflammatory amplification, fibrotic remodeling, dysregulated energy metabolism, aberrant cell proliferation, endothelial-mesenchymal transition, and ferroptotic cell death. Furthermore, we evaluate advances in bromodomain and extraterminal protein inhibitors across preclinical and clinical research, highlighting agents that demonstrate anti-inflammatory, antifibrotic, and cardioprotective efficacy in animal models of cardiovascular disease. By integrating mechanistic and translational evidence, this review provides a framework for understanding bromodomain and extraterminal proteins in cardiovascular diseases and guides the rational design of targeted therapies.