Abstract
This study aimed to establish a blood vessel model within a hollow fiber bioreactor to evaluate the impact of high and fluctuating glucose levels on human umbilical vein endothelial cells (HUVECs) under laminar shear stress (LSS). HUVECs were cultured for 48 h in normal (5 mM), high (20 mM), and variable (20 mM / 5 mM alternating every 24 h) glucose concentrations under LSS of 0.66 Pa. An automated medium replacement system was developed. The control cultures remained static. The analysis included cell viability via cytometric analysis, glucose consumption, lactate production via electroenzymatic methods, and the expression of 21 genes via qPCR. The percentage of apoptotic cells did not significantly differ across glucose concentrations under LSS. HUVECs favor glycolysis for energy regardless of LSS. Under LSS, the IL1B, CCL2, and SELE genes were upregulated under high-glucose conditions and downregulated under variable-glucose conditions. A few other genes related to inflammation, oxidative stress, cell adhesion and apoptosis were upregulated under high-glucose conditions. In conclusion, using the blood vessel model we effectively examined the impact of glucose profiles on HUVECs under LSS in a device replicating the cylindrical geometry of blood vessels. LSS and tubular cell arrangement might mitigate the adverse effects of variable glucose on endothelial cells.
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