Hypoxia regulate developmental coronary angiogenesis potentially through VEGF-R2- and SOX17-mediated signaling.

Background: The development of coronary vessels in embryonic mouse heart involves various progenitor populations, including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is known to regulate coronary growth from the SV, whereas VEGF-A/VEGF-R2 signaling controls growth from the endocardium. Previous studies suggest hypoxia might regulate coronary growth, but its specific downstream pathways are unclear.

Elabela and Apelin regulate coronary angiogenesis in a competitive manner.

APJ, a G-protein coupled receptor, regulates coronary angiogenesis in the developing mouse heart. However, the exact mechanism by which APJ regulates coronary angiogenesis from its dual ligands, ELABELA and APELIN, is unclear. Our study show that ELABELA and APELIN both stimulate angiogenic activities such as proliferation and sprouting outgrowth in explant cultures.

Hypoxia regulate developmental coronary angiogenesis potentially through VEGFR2- and SOX17-mediated signaling.

Background: Coronary vessels in embryonic mouse heart arises from multiple progenitor population including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is shown to regulate coronary growth from SV pathway within the subepicardium, whereas VEGF-A/VEGF-R2 pathways is implicated to regulate coronary growth from endocardium pathway. Our previous study show hypoxia as a potential signaling cue to stimulate overall coronary growth and expansion within the myocardium.