Emerging role of DYRK1A as a target in cardiovascular diseases (Review)

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, imposing a substantial burden on public health. Dual‑specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a conserved protein kinase involved in diverse biological processes, and its aberrant expression has been associated with multiple human diseases. Emerging evidence indicates that DYRK1A contributes to the pathogenesis of various CVDs. However, its context‑specific regulatory mechanisms and therapeutic potential in CVDs remain insufficiently characterized, limiting the development of targeted interventions. This review summarizes the roles of DYRK1A in three major CVDs: Myocardial infarction (MI), cardiomyocyte hypertrophy and pulmonary arterial hypertension (PAH) In MI, DYRK1A inhibits cardiomyocyte proliferation by suppressing cell cycle‑associated signaling pathways, including the retinoblastoma protein/E2f pathway, and modulating epigenetic mechanisms, thereby impairing cardiac repair. In cardiomyocyte hypertrophy, DYRK1A inhibits abnormal myocardial growth by antagonizing pro‑hypertrophic nuclear factor of activated T cells (NFAT) signaling via direct NFAT phosphorylation. In PAH, DYRK1A promotes pathological vascular remodeling by inducing pulmonary arterial smooth muscle cell hyperproliferation via the STAT3/Pim‑1/NFAT pathway and impairing endothelial cell function via the DYRK1A/peroxisome proliferator‑activated receptor γ/early growth response protein 1 pathway. The present review outlines the context‑dependent regulatory effects of DYRK1A in CVDs, which are either protective or pathogenic depending on the disease type and stage. In addition, it emphasizes the requirement for further mechanistic evaluation and the development of DYRK1A‑targeted strategies to advance the translational of DYRK1A as a disease‑specific therapeutic target in CVDs.