A model for aortic valve calcification
Calcific aortic valve disease is a common cardiac defect, particularly among the aging population. While several risk factors such as bileaflet valve structure and old age, have been identified, molecular mechanisms resulting in calcific aortic valve disease are still under active investigation. Bone morphogenetic protein signaling via the activin type I receptor (AcvRI) plays an important role both during physiological and pathological processes involving calcification, e.g. bone formation and heterotopic ossification. While AcvRI is required for normal cardiac valve development, its role in aortic valve disease is currently unknown. Here we propose to investigate how BMP signaling via AcvRI in endocardial cells regulates aortic valve development and unravel the mechanisms by which AcvRI contributes to calcific aortic valve disease. The proposed experiments will contribute to our understanding of pathogenetic mechanisms that result in calcific aortic valve disease in humans.