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But, what is the appropriate balance of growth factors required for capillary lumen formation?When added alone, the cells invaded the underlying gel, resulting in the formation of branching tubelike structures with widely patent lumenia.Thus, the antiproteolytic effect of TGF, which results from a large increase in PAI and a subsequent reduction in brinolysis, probably accounts in part for the observed reduction in lumen diameter.The observation that angiogenesis reects a perhaps delicate balance between competing inuences leads to a number of questions concerning the outcome when one of the processes dominates.These structures bear stricking resemblance to the large cysts that are found in some endothelial tumors in vivo. In conclusion, there must be an equilibrium between growth factors bFGF and VEGF and the antiangiogenic TGF in order for lumen formation to occur.When there is no angiogenesis, there is a balance between the inducers and the inhibitors in favor of the inhibitors, while when angiogenesis is observed the balance is shifted in favor of the inducers.Hypoxia is thought to be the primary reason for shifting the balance towards the vascular phenotype.The EC expression levels of endostatin were higher than those of pericytes.However, they both propose a more active involvement of nontumor cells in endostatin production.Contrary to the angiogenic switch hypothesis, this idea suggests a more dynamic role of the inhibitors in the angiogenic process, since, according to this scenario, the release of angiogenic inhibitors occurs simultaneously with EC migration and proliferation.Therefore, it is possible that both of the suggested scenarios are true.However, with each of these models the process of sprout extension leading to the formation of a capillary network has been simulated by tracking the path of the leading capillary tip.It is now recognized that these cells are playing an active part in angiogenesis, including cytokine production, cellular adhesion and detachment, and lumen formation. Of course much remains to be done before a quantitative understanding of angiogenesis is possible, and to conclude, we identify a number of processes for which mathematical models can shed light on the interplay between different factors controlling these processes.We list these in order of chronological dependency, ordered by the progression of angiogenesis, and as the reader will note, the list is merely a resynthesis of the material discussed earlier, but now with the emphasis on the underlying processes rather than the biochemical factors.Modeling the dynamics of each individual endothelial cell of the newlydeveloped capillary vessel also has the advantage that one can Fosfomycin calcium incorporate processes such as mitosis, cell death, and lumen formation.Once blood ow is restored, there is a period of vascular reorganization.Redundant capillaries regress, a process which requires cell death, whereas other capillaries develop into mature, Silver sulfadiazine quiescent vessels with increasing diameters and ECM deposition.The mechanisms of vascular maturation are unclear. Incorporation of cell death and vacuole development into a model can help identify the important factors involved in capillary regression and vasculature maturation.It has been observed experimentally that most of the EC proliferation is conned just behind the sprout tip.However, at a distance from the parent vessel the TAF concentration is higher, which stimulates the release of more inhibitor as well.

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