How do immune cells drive heart valve disease?

Heart valve stenosis is a common and life-threatening disease in which the heart valves become thickened and stiff, restricting blood flow and ultimately leading to heart failure. Although millions of people are affected worldwide, the biological mechanisms driving disease progression remain poorly understood, limiting the development of effective therapies. Progress has also been hindered by the lack of suitable animal models. Mouse models rarely develop spontaneous valve stenosis, while large animal models such as sheep and pigs are costly and difficult to use for mechanistic studies and drug discovery. Recently, zebrafish were discovered to develop age-associated heart valve stenosis, providing a powerful new model for investigating this disease. This project will establish and characterise this emerging model and use it to address a fundamental unanswered question: how do immune cells contribute to the onset and progression of heart valve stenosis? By combining state-of-the art ultrasound imaging, high-resolution confocal imaging, and molecular biology, the project will provide new insights into how inflammation drives heart valve disease and may identify novel therapeutic targets for future treatments.