Valvular endothelial cells (VEC)
Valvular endothelial cells (VEC) represent the cell layer that covers the leaflets, in line with the endothelium from the entire cardiovascular system. However, VEC are phenotypically different from other cardiovascular endothelial cells, probably due to the fact that they interact with VIC to maintain the integrity of valve tissues and potentially, also to mediate disease (26). They are highly specialized endothelial cells: usually endothelial cells in vascular tissues are typically elongated in the direction of blood flow, but on the leaflets they have a circumferential arrangement to support leaflet stresses and mechanical forces (30). As all endothelial cells, VEC are crucial to function as a barrier, regulating interactions between blood flow and VICs, including metabolic and inflammatory processes (31).
VEC may also exhibit differences phenotypes depending on their location on the valve leaflets (32). Endothelial cell production of nitric oxide (NO) is an important crosstalk to maintain VIC quiescent and endothelial injury has been proposed to be an initiating factor for calcified aortic valve disease (33). VEC are also responsible for the non-thrombogenic proprieties of the leaflets, playing an important immune and inflammatory role (34). VEC are also capable of responding to mechanical stimuli, with a flow-mediating mechanotransduction process being responsible for the activation of protective or pathological pathways (35).