Hypoxia differentially affects coronary vessel formation during heart development

While hypoxia is a known stimulus for angiogenic sprouting, the exact mechanisms by which hypoxia - and resultant increased VEGFA - influences vessel growth in the heart are not clearly delineated. We used a genetic mouse model to mimic hypoxia through ectopic stabilisation of myocardial HIFα.

This enabled us to study the consequences of hypoxia without vascular depletion. Changes in coronary ECs in these hearts relative to littermate controls were assessed by single cell RNA-sequencing. This identified increased angiogenic gene expression and a shift towards a non-proliferative, migratory tip cell phenotype.