Targeting the Endocardium to Augment Neovascularisation of the Ischaemic Heart

Following myocardial infarction (MI), survival of existing and regenerated tissue depends upon formation of new coronary blood vessels, yet endogenous neovascularisation is poorly understood. In the embryo, coronary vessels form from three distinct cellular sources. Our work has demonstrated a significant role for each of these sources in de novo vessel formation post-MI, including by induced hypertrabeculation-compaction of the redeployed endocardium. An endocardial-specific adult-inducible cre mouse line is needed to definitively prove origin and to drive enhanced endocardium-derived neovascularisation. A potentially useful Cre (Npr3CreER) has recently been described but it’s suitability for use in adult MI studies is unclear. We will import the line from our collaborator and test the Cre in our MI model. In parallel, we will analyse and validate our recent RNAseq data set to explore alternative endocardial markers that may enable the identification and/or derivation of an improved endocardial Cre line.