Developmental Pathways and Aortic Valve Calcification

Calcific aortic valve disease (CAVD) has been associated with activation of molecular pathways involved in both heart valve and bone development. There is increasing evidence that developmental pathways are reactivated during disease and also that the process of calcification during CAVD may mimic that of normal endochondral bone formation. A number of different signaling pathways and transcription factors play essential roles both in heart valve development and bone formation. Notably, these mechanisms have also been implicated in the pathogenesis of CAVD. Although studies in human, mouse, and porcine models demonstrate conserved mechanisms in CAVD, the individual contributions to pathogenesis and requirements of each pathway for the development of aortic valve calcification are not fully understood. Furthermore, the crosstalk among these signaling pathways, although hypothesized, remains unknown. The goal of this chapter is to review pathways involved in development of both heart valves and bone and their reactivation in CAVD.