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Unraveling the VEGF-induced angiogenic switch by in vivo vascular transcriptome analysis
Project funded by own resources |
Project title |
Unraveling the VEGF-induced angiogenic switch by in vivo vascular transcriptome analysis |
Principal Investigator(s) |
Banfi, Andrea
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Project Members |
Gianni' Barrera, Roberto
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Organisation / Research unit |
Departement Biomedizin / Cell and Gene Therapy (Banfi) |
Project start |
01.01.2012 |
Probable end |
30.06.2014 |
Status |
Completed |
Abstract |
Arteriosclerosis, leading to the occlusion of arteries in the heart and legs, is the most common cause of death and disability in developed countries. Vascular Endothelial Growth Factor (VEGF) induces the growth of new blood vessels, which may improve the blood flow in affected tissue. However, VEGF can either generate normal and functional blood vessels or cause the growth of vascular tumors (angiomas), depending on its amount in the treated tissues. Therefore, in order to minimize toxic effects and increase its therapeutic efficacy, it would be important to understand how different VEGF doses can cause normal or aberrant vascular growth. In this project we aim at dissecting the molecular pathways involved in the switch between normal and aberrant VEGF-induced angiogenesis and elucidating the mechanisms by which PDGF-BB-recruited pericytes normalize angiogenesis. We will take advantage of a unique angiogenesis model in skeletal muscle in which microenvironmental VEGF dose and pericyte recruitment can be controlled precisely and independently. Molecular pathways differentially regulated in the transition between normal and aberrant angiogenesis will be identified using in vivo transcriptome analysis on vascular cells isolated by laser capture microdissection after angiogenic induction with specific VEGF levels alone or together with PDGF-BB co-expression. The regulatory network governing the switch between normal and aberrant angiogenesis by VEGF will be identified using a series of specialized enrichment and cluster analyses in collaboration with F. Hoffmann-La Roche Ltd. The regulation of expression of target genes during the different stages of angiogenesis will be validated by qRT-PCR and immunofluorescence staining. These experiments are expected both to provide fundamental knowledge on mechanisms of vascular growth and maturation and to identify novel molecular targets to improve safety and efficacy of therapeutic angiogenesis. |
Financed by |
University funds
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Published results () |
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ID |
Autor(en) |
Titel |
ISSN / ISBN |
Erschienen in |
Art der Publikation |
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2419047 |
Taylor, Jennifer; Banfi, Andrea |
European Perspectives Funding: Swiss Heart Foundation Research Grant 2012 - Andrea Banfi, MD |
0009-7322 |
Circulation |
JournalItem (Kommentare, Editorials, Rezensionen, Urteilsanmerk., etc. in einer wissensch. Zeitschr. |
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11/05/2024
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