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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bcl-2-Like Protein 11 / metabolism
  • Caspase 3 / metabolism
  • Cell Survival
  • Cells, Cultured
  • Collagen Type IV / metabolism
  • Embryo, Mammalian / cytology
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Kidney / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cell Leukemia Sequence 1 Protein / deficiency
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
  • Neovascularization, Physiologic / physiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • bcl-2 Homologous Antagonist-Killer Protein / deficiency
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / deficiency
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Bcl-2-Like Protein 11
  • Collagen Type IV
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Platelet Endothelial Cell Adhesion Molecule-1
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Caspase 3