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Targeted regulation of angiogenesis by nanoparticle-guided specific interference with endothelial signalling molecules - Krötz/Mannell

Formation of new blood vessels, angiogenesis, is important for both physiological and pathophysiological processes and its induction or inhibition could be used for therapies aiming at for instance supporting ischemic areas with oxygen or stop tumour growth respectively. The different steps underlying the angiogenic process, such as endothelial cell proliferation, migration and the organized formation of new tubes are highly dependent on the vascular endothelial growth factor (VEGF), which is up regulated during ischemic conditions. We have previously shown that the tyrosine phosphatase SHP-2 is critical for angiogenesis by regulating angiogenic signaling (Mannell et al., 2008), thus constituting a promising target for angiogenic therapy. The aim of this study is to investigate whether SHP-2 is part of the ischemic response leading to enhanced vessel formation and to apply this to therapeutically relevant in vivo situations, such as ischemia. This shall be achieved by using the technique of nano particle containing microbubbles for magnetically site-directed delivery of nucleic acid inhibitors and mutant forms of SHP-2 in vivo.

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