Targeting DYRKs in Cardiovascular Diseases: From Biological Mechanisms to Therapeutic Translation.

Cardiovascular diseases (CVDs) remain the leading cause of mortality globally, characterized by myocardial injury, pathological structural remodeling, and progressive deterioration of cardiac function. Clinical manifestations include post-infarct functional impairment, pathological cardiac hypertrophy, interstitial fibrosis, malignant arrhythmias, and end-stage heart failure. Although the dual-specificity tyrosine-regulated kinase (DYRK) family has been extensively investigated in cancer and neurodegenerative disorders, emerging evidence highlights DYRKs as critical upstream regulators in a wide spectrum of cardiovascular pathological processes. However, current research is largely confined to individual isoforms or isolated signaling pathways, lacking systematic integration of isoform-specific functions, dose- and spatiotemporal-dependent effects, as well as bidirectional regulatory roles in chronic cardiac remodeling. This review systematically summarizes the molecular mechanisms of the DYRK family across major cardiovascular disease models, with particular emphasis on the functional specificity of distinct DYRK isoforms and their translational potential as therapeutic targets. We further provide an integrated theoretical framework to facilitate the development of isoform-selective, context-dependent precision therapies for cardiovascular diseases.