We Aim to Determine the Regulatory Mechanisms Involved in the Switch Between Normal and Aberrant Angiogenesis Induced by Different Doses of Vascular Endothelial Growth Factor

The 2 major prerequisites to pursue such a systematicinvestigation are a highly controlled angiogenesis modeland a technique that allows specific isolation of affectedvascular cells from their microenvironment in tissue.Therefore, Dr Banfi and his coresearchers have combineda unique cell-based platform for controlled in vivo geneexpression with laser capture microdissection to perform astage-specific and VEGF dose-dependent analysis of thevascular messenger RNA and microRNA transcriptome.The group has developed a unique model of VEGFdose-dependent angiogenesis in mouse skeletal musclebased on the implantation of monoclonal populations ofretrovirally transduced myoblasts, which ensure homoge-neous expression of a specific VEGF dose, alone or togetherwith PDGF-BB, in the microenvironment around eachengrafted fibre. The clinically relevant tissue for peripheralartery disease (ie, skeletal muscle) is used, in the absenceof ischaemia, to avoid the confounding factors of inflam-mation and upregulated endogenous factors. Normal andaberrant vascular structures developing in the areas ofimplantation over a previously defined time course aremicrodissected at the International Centre for GeneticEngineering and Biotechnology, Trieste, Italy. Total RNA