Recent Advances in Deciphering Normal and Diseased Aortic Valve Biology Using Transcriptomic Technologies

Calcific aortic valve disease (CAVD) is a growing global health burden, with no approved pharmacological treatments to date, indicating a substantial therapeutic gap and the need for deeper insight into its underlying mechanisms. Transcriptomic approaches, particularly RNA sequencing (RNAseq) and single-cell sequencing (scRNAseq), are emerging as powerful tools for unravelling the complex biology of the aortic valve (AV) in both normal and diseased states. This review summarises recent advances in our understanding of AV structure and function, with emphasis on valvular cell plasticity, heterogeneity and intercellular interactions—especially between valvular endothelial cells (VECs) and monocytes under physiological and pathological conditions. We further underscore the importance of characterising baseline molecular and cellular processes in the healthy AV to properly interpret disease-associated alterations. By integrating recent transcriptomic findings, this review identifies key molecular targets and prioritises them for validation through wet-lab experiments, with the ultimate goal of informing the development of effective therapies for CAVD.