Figure 5

Shear stress modulates the endothelial bioenergetic pathway. Panel A and B Enzimatic pathways of glycolysis and Krebb's cycle. Note the change in the expression of genes encoding for the key regulator enzymes of glucose metabolism and how the exposure to flow greatly favoured the more efficient aerobic pathway. The gene array data were confirmed by measurements of glucose consumption versus lactate production in DIV-BBB model developed with and without l endothelial exposure to intraluminal flow (Panel C). Comparative analysis of the expression level of key enzymes regulating the glycolitic and the aerobic (Krebb's cycle) pathways strongly supported the gene array data (Panel D). Note that the lactate production/glucose consumption ratio measured in the flow-exposed in vitro BBB modules was ≈ 1. Complete anaerobic metabolism would produce 2 lactates/glucose (ratio = 2) thus, indicating that at least 50% of the glucose consumed underwent aerobic metabolism.