An investigation into the regulatory pathways controlling coronary arterial differentiation

Occlusion of a coronary artery leaves perfusion dependent on collateral arteries which are rarely sufficient, and therefore often results in significant myocardial ischemia and subsequent tissue damage.

Although reperfusion therapy can restore some blood flow, ischemic damage and debris often lead to obstructed flow and poor outcomes.

Recovery after occlusion could be improved by increased quantity and quality of neovascular growth around the infarct, and by greater numbers of functional collateral arteries.

However, our ability to engender these responses is limited by an incomplete understanding of vascular regulation generally, and arterial differentiation specifically.

Here, I will characterize a cohort of novel arterial enhancers regulating key coronary arterial genes and use them to determine the upstream transcriptional and signalling pathways directing arterial growth during development, neovascularization and collateral formation.

This work will increase our understanding of how arterial behaviour is regulated and identify novel strategies to induce and improve arterial growth to prevent ischemia and stimulate tissue repair.