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. 2022 Dec 9;7(50):45849–45866. doi: 10.1021/acsomega.2c05599

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© 2022 The Authors. Published by American Chemical Society

Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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Signaling pathways involved in gasotransmitter-mediated angiogenesis. (A) The H₂S stimulates activation of the PI3K/Akt pathway that mediates angiogenesis by activating the eNOS pathway. The H₂S also activates the K_ATP channel, causing hyperpolarization of the membrane, leading to a decrease in intracellular Ca²⁺. This further promotes the relaxation of blood vessels in smooth muscle cells. (B) NO generated by eNOS induces activation of the sGC pathway, which catalyzes the conversion of GTP to cGMP and further promotes downstream signaling to mediate angiogenesis. (C) CO stabilizes HIF1α through the HSP 90 protein, which protects the HIF factor from degradation. This promotes the binding of HIF1α and HIFβ to HRE, which subsequently mediates the expression of VEGF.