Hypoxia regulate developmental coronary angiogenesis potentially through VEGF-R2- and SOX17-mediated signaling
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Summary
This summary is machine-generated.Hypoxia regulates embryonic heart vessel development through SOX17 and VEGF-R2 pathways. Stabilizing HIF-1α in mice accelerated coronary growth, highlighting these molecular mechanisms in angiogenesis.
Area Of Science
- Cardiovascular Biology
- Developmental Biology
- Molecular Medicine
Background
- Embryonic heart coronary vessel development involves multiple progenitor cells.
- Specific signaling pathways like ELA/APJ and VEGF-A/VEGF-R2 regulate growth from different origins.
- The role of hypoxia in regulating coronary growth and its downstream pathways remain incompletely understood.
Purpose Of The Study
- To investigate the role of hypoxia in embryonic coronary angiogenesis.
- To identify the specific downstream molecular pathways mediating hypoxia's effects on coronary vessel development.
Main Methods
- Utilized a mouse model with myocardial knockout of von Hippel Lindau (VHL) protein to stabilize HIF-1α.
- Examined gene expression of VEGF-R2 and SOX17 in hypoxic conditions (in vitro) and in VHL cKO hearts (in vivo).
- Assessed the impact of endocardial SOX17 knockout on coronary growth.
Main Results
- Stabilization of HIF-1α disrupted normal coronary angiogenesis, leading to accelerated growth patterns.
- Hypoxia increased VEGF-R2 expression in coronary endothelial cells.
- SOX17 expression was upregulated in VHL cKO hearts, and its knockout impaired coronary growth.
Conclusions
- Hypoxia plays a significant role in regulating developmental coronary growth.
- VEGF-R2 and SOX17 signaling pathways are identified as potential mediators of hypoxia's effects.
- These findings contribute to understanding the molecular mechanisms of coronary vessel development.