While angiopoietin-1/Tie-2 signaling promotes vascular quiescence, the proinflammatory protein Ang2 destabilizes the vasculature at sites of vessel remodeling by antagonizing the binding of Ang1 to Tie-2. Ang2 primes the endothelium to respond to pro-inflammatory cytokines, such as VEGF, TNF-a and IL-1b. In this manner Ang2 triggers an inflammatory response by activating the endothelium, inducing endothelial permeability and extravasation of inflammatory cells and thereby contributes to premature atherosclerosis. We anticipate that targeting of Ang2 to WPBs provides a mechanism to reduce circulating levels of Ang2 thereby promoting vascular quiescence. In the absence of WPBs, due to lack of VWF, Ang2 levels increase and destabilize the vasculature allowing for vascular remodeling. The decrease in secreted IL-8 from IL-1b stimulated KLF2 cells might result from this decreased sensitivity to cytokines; however the amount of secreted IL-6 is still the same in KLF2 cells. These findings suggest that KLF2 expressing endothelial cells are less prone to vascular remodeling, inflammation and ultimately atherosclerosis. In contrast, at sites of disturbed flow, where endothelial cells do not express KLF2, Ang2 can be released from the WPBs, promoting inflammation and vascular remodeling and therefore making these sites more susceptible to premature atherosclerosis and plaque neovascularization. Our findings on the lack of Ang2 in KLF2- transduced endothelial cells together with previous observation on down-regulation of Ang2 levels by flow provide a mechanism to stabilize newly formed vasculature by reducing the synthesis of vessel-destabilizing Ang2. Loss of function of the dimeric mutants is attributed to excessive dynamics or ‘breathing motion’ at the ‘tight’ dimer interface, which compromises the integrity of the active sites. Accordingly, the buttressing of two dimeric units together to form the homotetrameric structure is thought to stabilize the tight dimer interface, including the key active site residues. By contrast, structural characterization of DHDPS from plants is limited to a single study of the enzyme from the wild tobacco plant, Nicotiana sylvestris. This study shows that N. sylvestris DHDPS also forms a homotetramer, but in a ‘back-to-back’ arrangement opposite in orientation to the typical bacterial tetrameric form. Consequently, the allosteric sites that bind AbMole BioScience Life Science Reagents lysine and mediate feedback inhibition are located in the interior of the tetramer rather than on the outside of the structure as observed for E. coli DHDPS. However, the N. sylvestris enzyme is the only plant DHDPS structure determined to date. The unique quaternary architecture observed in the crystal structure of N. sylvestris DHDPS has not yet been confirmed in other plant species or validated in aqueous solution; and surprisingly, the structural coordinates of the N. sylvestris enzyme are not available in the Protein Data Bank.