Abstract
Haemodynamic forces have a synergistic effect on endothelial cell (EC) morphology, proliferation, differentiation and biochemical expression profiles. Alterations to haemodynamic force levels have been observed at curved regions and bifurcations of arteries but also around struts of stented arteries, and are also known to be associated with various vascular pathologies. Therefore, curvature in combination with stenting might create a pro-atherosclerotic environment compared with stenting in a straight vessel, but this has never been investigated. The goal of this study was to compare EC morphology, proliferation and differentiation within in vitro models of curved stented peripheral vessel models with those of straight and unstented vessels. These models were generated using both static conditions and also subjected to 24 h of stimulation in a peripheral artery bioreactor. Medical-grade silicone tubes were seeded with human umbilical vein endothelial cells to produce pseudovessels that were then stented and subjected to 24 h of physiological levels of pulsatile pressure, radial distention and shear stress. Changes in cell number, orientation and nitric oxide (NO) production were assessed in straight, curved, non-stented and stented pseudovessels. We report that curved pseudovessels lead to higher EC numbers with random orientation and lower NO production per cell compared with straight pseudovessels after 24 h of biomechanical stimulation. Both stented curved and stented straight pseudovessels had lower NO production per cell than corresponding unstented pseudovessels. However, in contrast to straight stented pseudovessels, curved stented pseudovessels had fewer viable cells. The results of this study show, for the first time, that the response of the vascular endothelium is dependent on both curvature and stenting combined, and highlight the necessity for future investigations of the effects of curvature in combination with stenting to fully understand effects on the endothelial layer.