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Cell Death Differ. 2016 Aug;23(8):1371-9. doi: 10.1038/cdd.2016.20. Epub 2016 Mar 4.

Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1.

Author information

1
Development and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.
2
Department of Medical Biology, University of Melbourne, 1G Royal Parade, VIC, Australia.
3
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.
4
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, Münster D, Germany.
5
Faculty of Medicine, University of Münster, Münster D, Germany.
6
Cell Signalling and Cell Death Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.

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.

PMID:
26943318
PMCID:
PMC4947668
DOI:
10.1038/cdd.2016.20
[Indexed for MEDLINE]
Free PMC Article

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