VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC

Figure 5

ox-VLDL-dependent EC dysfunction: schematic representation of the eNOS and iNOS involvement. The activity of eNOS (yellow) and iNOS (red) dimers are sketched. The coupled (native) eNOS is featured by the utilisation of substrates such as L-Arg and O₂ and production of NO, in the presence of the cofactor calmodulin (CAM) and under condition of Ser1177 phosphorylation, promoting activity (white cell background). ox-VLDL triggers eNOS phosphorylation at residue Thr495, with dephosphorylation of Ser1177: under these conditions, the eNOS is uncoupled (U-eNOS) and results in the generation of O₂^−•. In parallel, high level of iNOS biosynthesis occurs, leading to increased ROS and RNS production and resulting in the down-modulation of mitochondrial function (gray background).