Cardiovasc Res. 2026 Oct 31:cvag239. doi: 10.1093/cvr/cvag239. Online ahead of print.
ABSTRACT
The human genome is highly organized within the nucleus and is remodeled across physiological and disease states. Enabled by rapidly advancing technologies for mapping three-dimensional chromatin architecture, recent works have begun to define how three-dimensional chromatin architecture changes in the cardiovascular system and how these changes influence gene regulation. Here, we summarize the hierarchical folding features of 3D chromatin architecture and discuss major sequencing- and imaging-based strategies for mapping chromatin organization, including emerging single-cell and multimodal approaches that extend static 3D maps toward a spatiotemporal 4D nucleome perspective. We highlight how genetic variants, structural variants, mechanical forces, metabolic-inflammatory stress and lamina-genome disruption reshape chromatin topology in heart development, aging and cardiovascular diseases. Representative examples across cardiovascular diseases illustrate how altered enhancer-promoter communication, chromatin insulation and nuclear positioning can contribute to pathogenic gene regulation. Finally, we discuss the therapeutic potential of 3D genome engineering and propose that the near-term translational value of cardiovascular 3D genomics lies primarily in improving disease-gene nomination and therapeutic target prioritization, while direct manipulation of chromatin architecture remains a promising but technically challenging frontier.
PMID:42963079 | DOI:10.1093/cvr/cvag239