A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands
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{"title"=>"A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands", "type"=>"journal", "authors"=>[{"first_name"=>"Lindsay E", "last_name"=>"Clegg"}, {"first_name"=>"Feilim", "last_name"=>"Mac Gabhann"}], "year"=>2017, "source"=>"PLOS Computational Biology", "identifiers"=>{"doi"=>"10.1371/journal.pcbi.1005445"}, "id"=>"45b4ce51-f1f4-3d95-8fa8-95b12ac67383", "abstract"=>"Author summary Angiogenesis, the growth of new blood vessels from the existing vasculature, is critical for maintenance of health and response to injury. In ischemic disease, this process is impaired, but therapies targeting a key family of proteins, the vascular endothelial growth factors (VEGF), have failed to translate clinically. This suggests a need for deeper understanding of the complex regulation underlying angiogenic signaling. Here, we translate a previously developed and validated model of VEGF family signaling into a human, whole-body framework. The different splice isoforms of VEGF and the related PlGF proteins have different affinities for the extracellular matrix (ECM) and the co-receptor Neuropilin-1. Using our model, we examine the effect of these different binding properties on the distribution of each isoform in tissue, and subsequent receptor signaling. The model predicts isoform-specific receptor activation that is consistent with observed vascular phenotypes in mice expressing a single VEGF isoform; non-ECM-binding isoforms lead to signaling that promotes cell proliferation, while strong ECM-binding promotes migratory signaling and increased vessel branching. This understanding is critical for design of biomaterials that manipulate VEGF-ECM binding to control growth factor delivery, and for understanding of splicing-induced changes in VEGF family signaling in different tissues and in disease.", "link"=>"http://www.mendeley.com/research/computational-analysis-vivo-vegfr-activation-multiple-coexpressed-ligands", "reader_count"=>1, "reader_count_by_academic_status"=>{"Researcher"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "reader_count_by_subdiscipline"=>{"Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}


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  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"40", "xml_views"=>"5", "html_views"=>"723"}
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