Zebrafish in Cardiovascular Disease Research: from Model to Application.

Cardiovascular diseases (CVDs) remain a major cause of global morbidity and mortality, yet their complex pathophysiology is difficult to recapitulate in conventional mammalian models fully. Compared with traditional mammalian and in vitro systems, zebrafish offer several distinct advantages for CVD research. Their small size, high fecundity, and rapid development make them particularly suitable for high-throughput screening, while embryonic transparency enables real-time, noninvasive imaging of dynamic cardiac processes. High genetic homology with humans, together with facile genetic manipulation, further supports their utility in modeling cardiovascular disorders. In addition, their unique capacity for cardiac regeneration provides a valuable platform for regeneration studies. A wide range of endogenous and exogenous zebrafish models have successfully recapitulated key features of human CVDs, thereby facilitating mechanistic investigation and the identification of critical signaling pathways. Zebrafish also enable cost-efficient phenotypic screening and have contributed substantially to early-stage drug discovery and cardiotoxicity assessment. In summary, despite anatomical differences from mammals, zebrafish combine genetic tractability, phenotypic fidelity, and screening efficiency, underscoring their value in advancing drug discovery and therapeutic development for CVDs.