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.
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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.
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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).
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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
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DOI: https://doi.org/10.1038/s44161-023-00279-x