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. Author manuscript; available in PMC: 2013 Apr 9.
Published in final edited form as: Circ J. 2011 Nov 10;75(12):2722–2730. doi: 10.1253/circj.cj-11-1124

Figure 2.

Figure 2

Schematic of recently identified endothelial signaling modules that can be activated by s- or d-flow. d-flow induces production of ROS such as .O2− and ONOO− via activation of NADPH oxidase and causes endothelial dysfunction. BMP-4 is generated by d-flow and activates NADPH oxidase. ROS can then activate NF-κB and induce ICAM-1 expression and inflammation. d-flow can also induce PKCζ activation, leading to EC apoptosis via p53-SUMOylation and to inflammation via ERK5 phosphorylation, which downregulates eNOS expression. On the other hand, s-flow, through activation of ERK5, increases the activity of PPARs and KLF2, which are responsible for inducing anti-inflammatory responses. (See text for details.)