Chemogenetic ablation and regeneration of arterial valve in zebrafish

Abstract

Aortic valve diseases are prevalent and severe cardiovascular conditions with limited treatment options beyond surgical intervention. The ability to regenerate aortic valves would revolutionize the management of these diseases. Utilizing the zebrafish model, which possesses remarkable regenerative capacities, we developed a chemogenetic arterial valve ablation model using a zebrafish-codon optimized nitroreductase. We found that arterial valve ablation led to blood regurgitation and impaired cardiac function, which are commonly associated with aortic valve diseases. Following ablation, zebrafish arterial valve could fully regenerate and restore valvular and cardiac function. Moreover, suppression of blood flow significantly impedes valve regeneration, indicating the importance of hemodynamic forces in this process. Our research has successfully established a robust aortic valve injury model to study the cellular and molecular mechanisms underlying its regeneration process which will facilitate the development of innovative therapeutic strategies tailored for aortic valve diseases.