Soluble perlecan domain i enhances vascular endothelial growth factor-165 activity and receptor phosphorylation in human bone marrow endothelial cells

<p>Abstract</p> <p>Background</p> <p>Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, <it>in vitro</it>. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF₁₆₅) enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, <it>in vitro</it>.</p> <p>Results</p> <p>In solution, PlnDI binds VEGF₁₆₅in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF₁₆₅mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF₁₆₅alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF₁₆₅reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951), and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF₁₆₅but not VEGF₁₂₁significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2.</p> <p>Conclusions</p> <p>Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF₁₆₅can enhance VEGFR-2 signaling and angiogenic events, <it>in vitro</it>. We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, <it>in vivo</it>.</p

I love to hate you: Loyalty for disliked brands and the role of nostalgia

Brand loyalty has been a popular research area for the previous decades, and concepts such as satisfaction, trust, repurchase behavior and positive brand image have been associated with brand loyalty as antecedents of the concept. This study investigates how much satisfaction actively is required for the development of brand loyalty, focusing on the cases in which loyalty is retained in spite of being disliked. This qualitative study employs 14 semi-structured interviews and for the first time in the literature reveals that nostalgia may play an important role in maintaining an otherwise failed brand relationship, among other factors previously noted