The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions
Abstract
The 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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000606515Publication status
publishedExternal links
Journal / series
AngiogenesisVolume
Pages / Article No.
Publisher
SpringerSubject
Angiogenesis; Endothelial cell; EC proliferation; Hindlimb ischemia; Stroke; TumorOrganisational unit
09560 - De Bock, Katrien / De Bock, Katrien
09499 - Bohacek, Johannes / Bohacek, Johannes
09711 - Moor, Andreas / Moor, Andreas
Funding
208041 - Endothelial metabolism to promote muscle revascularization and regeneration (SNF)
ETH-20 19-1 - A cross‐disciplinary, data‐driven approach to predict stress resilience from large‐scale behavioral, molecular and neural activity data (ETHZ)
172889 - Dissecting stress-induced molecular changes in circuits underlying anxiety (SNF)
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Is new version of: https://doi.org/10.3929/ethz-b-000591166
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