Generating new transgenic models to study the coronary vasculature
Coronary endothelial cells (ECs) are known to be developmentally heterogeneous, with multiple origins. Neovascularisation of the ischaemic heart recapitulates, in part, the embryonic mechanisms of coronary vessel growth, but with key differences. There is currently a lack of understanding of the molecular pathways that regulate coronary vessel growth during development and repair. Sarah De Val, our collaborator, has characterized a number of endothelial gene enhancers that act as classical response elements downstream of distinct regulatory pathways. We confirmed that activity of these enhancers is modulated in response to myocardial infarction. The aim of our project was to generate a range of fluorescent enhancer reporters to delineate the contribution of the endocardial- and sinus venosus-derived lineages, and to label angiogenic, as well as venous and lymphatic ECs. Many of these lines have now been generated and are proving valuable in determining the underlying mechanisms of de novo vasculogenesis, angiogenesis and lymphangiogenesis, during development and towards regeneration of the infarcted heart.