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. 2022 Aug 19;10:933474. doi: 10.3389/fcell.2022.933474

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Copyright © 2022 Flournoy, Ashkanani and Chen.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The signaling pathways involved in angiogenesis. (A) At the front of a sprouting vessel, (B) VEGF binds to VEGFR on tip cells. VEGFR activation induced the expression of Dll4. Dll4 on the tip cells binds to Notch on stalk cells. Notch signaling in stalk cells downregulates the expression of VEGFR2/3 in stalk cells. (C) VEGF-VEGFR and FGF-FGFR signaling promote pro-angiogenic signals, cell proliferation, and cell survival. PDGF-PDGFR binding leads to vessel sprouting and stabilization. Notch interacts with Dll4 in a feedback loop to regulate cell migration and proliferation. Fibronectin and laminin bind to integrins to promote endothelial cell proliferation, survival, migration, and tube formation. Various integrin isoforms promote angiogenesis through different overlapping pathways. MMPs degrade denatured collagen in the basement membrane.