Fractal parameters and vascular networks: facts & artifacts

<p>Abstract</p> <p>Background</p> <p>Several fractal and non-fractal parameters have been considered for the quantitative assessment of the vascular architecture, using a variety of test specimens and of computational tools. The fractal parameters have the advantage of being scale invariant, i.e. to be independent of the magnification and resolution of the images to be investigated, making easier the comparison among different setups and experiments.</p> <p>Results</p> <p>The success of several commercial and/or free codes in computing the fractal parameters has been tested on well known exact models. Based on such a preliminary study, we selected the code Frac-lac in order to analyze images obtained by visualizing the angiogenetic process occurring in chick Chorio Allontoic Membranes (CAM), assumed to be paradigmatic of a realistic 2D vascular network. Among the parameters investigated, the fractal dimension D_fproved to be the most robust estimator for CAM vascular networks. Moreover, only D_fwas able to discriminate between effective and elusive increases in vascularization after drug-induced angiogenic stimulations on CAMs.</p> <p>Conclusion</p> <p>The fractal dimension D_fis likely to be the most promising tool for monitoring the effectiveness of anti-angiogenic therapies in various clinical contexts.</p

Stable interaction between α5β1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1

During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could cross-talk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that α5β1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and α5β1 interact constitutively; α5β1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively α5β1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and α5β1 receptors that could cross-talk when Tie2/α5β1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that α5β1, but not αvβ3 activation, is essential to Ang-1–dependent angiogenesis in vivo

Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

Angiopoietin-1 can promote migration, sprouting, and survival of endothelial cells through activation of different signaling pathways triggered by the Tie2 tyrosine kinase receptor. ShcA adapter proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to the Ras/mitogen-activated protein kinase pathway. Here we report the identification of an interaction between the adapter protein ShcA and the cytoplasmic domain of Tie2 through in vitro co-immunoprecipitation analysis. Stimulation of endogenous Tie2 in endothelial cells with its ligand angiopoietin-1 increased its association with ShcA and phosphorylation of the adapter protein. The interaction requires the SH2 domain of ShcA and the tyrosine phosphorylation of Tie2 as shown by pull-down experiments. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA. Overexpression of a dominant-negative form of ShcA affects angiopoietin-1-induced chemotaxis and sprouting, although it has no effect on survival of endothelial cells. Furthermore, this mutant partially reduces the tyrosine phosphorylation of the regulatory p85 subunit of phosphatidylinositol 3-kinase. Together, our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1

A, b, c: variations of D, Vand Faccording to different treatments (FGF, Ang)

<p><b>Copyright information:</b></p><p>Taken from "Fractal parameters and vascular networks: facts & artifacts"</p><p>http://www.tbiomed.com/content/5/1/12</p><p>Theoretical Biology & Medical Modelling 2008;5():12-12.</p><p>Published online 17 Jul 2008</p><p>PMCID:PMC2490683.</p><p></p