The role of AP-1 in distinct cardiac cell types: Pathological repair and maladaptive remodeling

Activator Protein-1 (AP-1) is a dimeric transcription factor complex formed by dynamic combinations of members from the Jun, Fos, ATF, and MAF families. It plays a pivotal role in regulating cell-state decisions, including proliferation, apoptosis, differentiation, and inflammation. In the cardiovascular system, aberrant activation of AP-1 has been closely linked to pathological conditions such as atherosclerosis, cardiac hypertrophy, ischemia-reperfusion injury, and heart failure. Its functional outcomes are highly dependent on subunit composition, cell type specificity, upstream signaling, and the integration of microenvironmental signals. This review systematically explores the dynamic regulatory networks of AP-1 across distinct cardiac cell subsets, including cardiomyocytes, vascular smooth muscle cells, cardiac fibroblasts, cardiac endothelial cells, and cardiac macrophages. Emerging evidence highlights the multifaceted, spatiotemporally tuned, and cell-type-specific roles of AP-1 in cardiovascular pathology. Future studies leveraging single-cell multi-omics and epigenetic profiling will be essential to elucidate the precise mechanisms of AP-1 action in individual cell types, and to refine therapeutic strategies targeting AP-1, thereby offering novel insights into precision medicine for cardiovascular diseases.