Computing of Low Shear Stress-Driven Endothelial Gene Network Involved in Early Stages of Atherosclerotic Process

Figure 6

Representation of relations between CXCR4, TNFAIP3, and Caspase-8 in HUVECs under physiological and low shear stress. At physiological level (a), shear stress is able to downregulate CXCR4, limiting its role in XBP-1 stimulation with reduction of apoptotic activity of Caspase-8; in parallel, there is low interaction with MIF, reducing monocyte adhesion and trans-migration in vascular wall. TNFAIP3 is highly expressed and inhibits Caspase-8. This behavior changes when endothelial cells are subjected to low shear stress (b): CXCR4 is overexpressed, promoting its interaction with MIF and consequent increased monocyte adhesion. Furthermore, it stimulates XBP-1, with augmented apoptotic activity not counteracted by TNFAIP3, which is downregulated.

(a)

(b)