FIG. 5.

Matrix-specific regulation of endothelial nitric oxide synthase (eNOS) by shear stress. Shear stress results in calcium-dependent eNOS activation and eNOS phosphorylation through PKA and potentially Akt. Enhanced PKA signaling in cells on basement membrane proteins results in a large increase in NO production, whereas the lack of PKA signaling in cells on fibronectin hinders shear-induced NO production. Shear-induced eNOS expression is enhanced on fibronectin, potentially due to reduced negative feedback between NO and the transcription factor, nuclear factor-κB (NF-κB).