Heart valve development, maintenance, and disease: the role of endothelial cells

Abstract

Heart valves are dynamic structures that open and close during the cardiac cycle to maintain unidirectional blood flow throughout life. Insufficient valve function, commonly due to congenital malformations leads to disruptions in hemodynamics and eventual heart failure. Mature valve leaflets are composed of a heterogeneous population of interstitial cells and stratified extracellular matrix, surrounded by a layer of endothelial cells. This defined connective tissue "architecture" provides the valve with all the necessary biomechanical properties required to efficiently function while withstanding constant cyclic shear stress. Valvular endothelial cells (VECs) play essential roles in establishing the valve structures during embryonic development and are important for maintaining lifelong valve integrity and function. In contrast to a continuous endothelium over the surface of healthy valve leaflets, VEC disruption is commonly observed in malfunctioning valves and is associated with pathological processes that promote valve sclerosis and calcification. Increasing our understanding of the roles of VECs in development and disease has lead to promising advances in the development of endothelial cell-based therapies for treating valve disease.