Targeting the Notch ligand DLL4 in adult liver vessels induced transcriptional states associated with endothelial cell (EC) proliferation and sprouting. However, genetic and pharmacological inhibition of these angiogenic cell states did not prevent an abnormal vasculature and pathology in the liver, suggesting that transcriptional states do not always inform on the vascular phenotype and related pathophysiology.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Siebel, C. & Lendahl, U. Notch signaling in development, tissue homeostasis, and disease. Physiol. Rev. 97, 1235–1294 (2017). This review presents an overview of NOTCH signaling mechanisms, and their relevance in tissue homeostasis and disease.
Fernandez-Chacon, M., Garcia-Gonzalez, I., Muhleder, S. & Benedito, R. Role of Notch in endothelial biology. Angiogenesis 24, 237–250 (2021). This review summarizes the most important findings on the role of NOTCH in endothelial biology.
Noguera-Troise, I. et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444, 1032–1037 (2006). One of the first papers reporting that anti-DLL4 inhibits tumor growth, including of tumors resistant to anti-VEGF.
Yan, M. et al. Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6–7 (2010). This paper reported that anti-DLL4 causes vascular neoplasms, raising safety concerns about its use in the clinic.
Couch, J. A. et al. Balancing efficacy and safety of an anti-dll4 antibody through pharmacokinetic modulation. Clin. Cancer Res. 22, 1469–1479 (2016). This papers shows how anti-DLL4 related vascular toxicity can be decreased by modulating anti-DLL4 pharmacokinetics.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Fernández-Chacón, M. et al. Incongruence between transcriptional and vascular pathophysiological cell states. Nat. Cardiovas. Res. https://doi.org/10.1038/s44161-023-00272-4 (2023).
Rights and permissions
About this article
Cite this article
Transcriptional states do not always predict vascular function and pathology. Nat Cardiovasc Res 2, 498–499 (2023). https://doi.org/10.1038/s44161-023-00279-x
Published:
Issue Date:
DOI: https://doi.org/10.1038/s44161-023-00279-x
