Abstract
BackgroundCarotid artery geometry is important for recapitulating a pathophysiological microenvironment to study wall shear stress (WSS)-induced endothelial dysfunction in atherosclerosis. Endothelial cells (ECs) cultured with hydrogel have been shown to exhibit in vivo-like behaviours. However, to date, studies using hydrogel culture have not fully recapitulated the 3D geometry and blood flow patterns of real-life healthy or diseased carotid arteries. In this study, we developed a gelatin-patterned, endothelialized carotid artery model to study the endothelium response to WSS.ResultsTwo representative regions were selected based on the computational fluid dynamics on the TF-shaped carotid artery: Region ECA (external carotid artery) and Region CS (carotid sinus). Progressive elongation and alignment of the ECs in the flow direction were observed in Region ECA after 8, 16 and 24 h. However, the F-actin cytoskeleton remained disorganized in Region CS after 24 h. Further investigation revealed that expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was greatly increased in Region CS relative to that in Region ECA. The physiological WSS in the carotid artery system was found to stimulate nitric oxide (NO) and prostacyclin (PGI2) release and inhibit endothelin-1 (ET-1) release after 24-h perfusion experiments. The effective permeability (E.P) of fluorescein isothiocyanate (FITC)–dextran 40 kDa in Regions ECA and CS was monitored, and it was found that the turbulence WSS value (in Region CS) was less than 0.4 Pa, and there was a significant increase in the E.P relative to that in Region ECA, in which laminar WSS value was 1.56 Pa. The tight junction protein (ZO-1) production was shown that the low WSS in Region CS induced ZO-1-level downregulation compared with that in Region ECA.ConclusionsThe results suggested that the gelatin-based perfusable, endothelial carotid artery model can be effective for studying the pathogenesis of atherosclerosis by which flow dynamics control the endothelium layer function in vitro.
Highlights
Carotid artery geometry is important for recapitulating a pathophysiological microenvironment to study wall shear stress (WSS)-induced endothelial dysfunction in atherosclerosis
Two representative regions (Region carotid sinus (CS) and Region external carotid artery (ECA)) in the carotid artery model were selected for analysis under laminar and turbulent WSS, respectively
Under physiological WSS for 24 h, the carotid artery model facilitated the spreading of Endothelial cells (ECs) to form an endothelialized layer on the model channel surface
Summary
Carotid artery geometry is important for recapitulating a pathophysiological microenvironment to study wall shear stress (WSS)-induced endothelial dysfunction in atherosclerosis. We developed a gelatin-patterned, endothelialized carotid artery model to study the endothelium response to WSS Carotid artery diseases such as atherosclerosis are characterized by artery wall fibrosis and lipid accumulation,which involve the endothelial cell (EC) dysfunction [1]. Due to the difficulty in studying EC dysfunction in vivo, three-dimensional (3D) tissue-engineered vascular models were investigated These models can provide a multifactorial environment that is critical for EC functioning, but they often fail to reproduce carotid artery features, including geometry and blood perfusion, which can affect endothelial functions [5]. As EC dysfunction and flow disturbance at the early stage can manifest into atherosclerosis complications, it is important to develop a perfusion-based carotid artery model with carotid artery geometry to better understand pathophysiology [2]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
