title: Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1.
abstract: Angiogenesis is essential to match the size of blood vessel networks to the metabolic demands of growing tissues. While many genes and pathways necessary for regulating angiogenesis have been identified, those responsible for endothelial cell (EC) survival during angiogenesis remain largely unknown. We have investigated the in vivo role of myeloid cell leukemia 1 (MCL1), a pro-survival member of the BCL2 family, in EC survival during angiogenesis. EC-specific deletion of Mcl1 resulted in a dose-dependent increase in EC apoptosis in the angiogenic vasculature and a corresponding decline in vessel density. Our results suggest this apoptosis was independent of the BH3-only protein BIM. Despite the known link between apoptosis and blood vessel regression, this was not the cause of reduced vessel density observed in the absence of endothelial MCL1. Rather, the reduction in vessel density was linked to ectopic apoptosis in regions of the angiogenic vasculature where EC proliferation and new vessel growth occurs. We have therefore identified MCL1 as an essential survival factor for ECs that is required for blood vessel production during angiogenesis.
authors.affiliation: Development and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.|Department of Medical Biology, University of Melbourne, 1G Royal Parade, VIC, Australia.
authors.forename: E C
authors.initials: EC
authors.lastname: Watson
authors.affiliation: Department of Medical Biology, University of Melbourne, 1G Royal Parade, VIC, Australia.|Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.
authors.forename: L
authors.identifier: 0000-0002-4388-9642
authors.initials: L
authors.lastname: Whitehead
authors.affiliation: Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, Münster D, Germany.|Faculty of Medicine, University of Münster, Münster D, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Department of Medical Biology, University of Melbourne, 1G Royal Parade, VIC, Australia.|Cell Signalling and Cell Death Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Dewson
authors.affiliation: Development and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.|Department of Medical Biology, University of Melbourne, 1G Royal Parade, VIC, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Coultas
mesh_terms: D000818:Animals; D017209:Apoptosis; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000072224:Bcl-2-Like Protein 11; D024141:Collagen Type IV; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D053148:Caspase 3