Background: Carotid artery geometry is important for recapitulating a pathophysiological\nmicroenvironment to study wall shear stress (WSS)-induced endothelial\ndysfunction in atherosclerosis. Endothelial cells (ECs) cultured with hydrogel have been\nshown to exhibit in vivo-like behaviours. However, to date, studies using hydrogel\nculture have not fully recapitulated the 3D geometry and blood flow patterns of reallife\nhealthy or diseased carotid arteries. In this study, we developed a gelatin-patterned,\nendothelialized carotid artery model to study the endothelium response to WSS.\nResults: Two representative regions were selected based on the computational fluid\ndynamics on the TF-shaped carotid artery: Region ECA (external carotid artery) and\nRegion CS (carotid sinus). Progressive elongation and alignment of the ECs in the\nflow direction were observed in Region ECA after 8, 16 and 24 h. However, the F-actin\ncytoskeleton remained disorganized in Region CS after 24 h. Further investigation\nrevealed that expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular\nadhesion molecule-1 (ICAM-1) was greatly increased in Region CS relative to that in\nRegion ECA. The physiological WSS in the carotid artery system was found to stimulate\nnitric oxide (NO) and prostacyclin (PGI2) release and inhibit endothelin-1 (ET-1) release\nafter 24-h perfusion experiments. The effective permeability (E.P) of fluorescein isothiocyanate\n(FITC)â??dextran 40 kDa in Regions ECA and CS was monitored, and it was found\nthat the turbulence WSS value (in Region CS) was less than 0.4 Pa, and there was a\nsignificant increase in the E.P relative to that in Region ECA, in which laminar WSS value\nwas 1.56 Pa. The tight junction protein (ZO-1) production was shown that the low WSS\nin Region CS induced ZO-1-level downregulation compared with that in Region ECA.\nConclusions: The results suggested that the gelatin-based perfusable, endothelial\ncarotid artery model can be effective for studying the pathogenesis of atherosclerosis\nby which flow dynamics control the endothelium layer function in vitro.
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