Author:
Fan Zheng,Ardicoglu Raphaela,Batavia Aashil A.,Rust Ruslan,von Ziegler Lukas,Waag Rebecca,Zhang Jing,Desgeorges Thibaut,Sturman Oliver,Dang Hairuo,Weber Rebecca,Roszkowski Martin,Moor Andreas E.,Schwab Martin E.,Germain Pierre-Luc,Bohacek Johannes,De Bock Katrien
Abstract
AbstractThe molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1−/− mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1−/− mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation.
Funder
Swiss Federal Institute of Technology Zurich
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Clinical Biochemistry,Physiology
Reference82 articles.
1. Krock BL, Skuli N, Simon MC (2011) Hypoxia-induced angiogenesis: good and evil. Genes Cancer 2:1117–1133. https://doi.org/10.1177/1947601911423654
2. Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887. https://doi.org/10.1016/j.cell.2011.08.039
3. Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478. https://doi.org/10.1038/nrm2183
4. Gorski T, De Bock K (2019) Metabolic regulation of exercise-induced angiogenesis. Vasc Biol 1:H1–H8. https://doi.org/10.1530/VB-19-0008
5. Nishijima T, Torres-Aleman I, Soya H (2016) Chapter 11 - Exercise and cerebrovascular plasticity. In: Masamoto K, Hirase H, Yamada K (eds) Progress in Brain Research. Elsevier, pp 243–268
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