Development, homeostasis and regeneration of the cardiovascular system
The principle of redeploying embryonic mechanisms in the adult heart for cardiac repair
Myocardial infarction (MI) causes irreversible cell loss and scarring, leading to adverse remodelling and heart failure. Given the heart’s inadequate capacity for self-repair, significant effort has been invested in regenerative strategies to replace damaged muscle cells and revascularise the heart. Due to their fundamental role in heart development, epicardium-derived cells (EPDCs) have emerged as a population with potential to regenerate myocardium and coronary vasculature. The ability to revive ordinarily dormant EPDCs lies in the identification of key molecular cues used in embryonic heart development.
EPDCs: potential to regenerate the inured heart
Ongoing research seeks to augment the intrinsic (inadequate) regeneration in the adult mammalian heart based on:
i) understanding mechanisms which induce epicardial activation and influence EPDC fate.
ii) identifying key regulators of the embryonic epicardium and extrapolation of the relevant mechanisms to the adult heart.
iii) investigating mechanisms of embryonic coronary vessel formation and recapitulation for neovascularisation in the adult.
Epithelial to Mesenchymal Transition for Mobilisation of EPDCs and Regeneration
Sinus venosus sprouting during coronary vessel development
A role for Thymosin β4 in maintenance of healthy vasculature
Damage to the endothelial cells that line blood vessels causes accumulation of cholesterol, immune cell infiltration and destruction of muscle and elastic layers, to weaken the vessel. Rupture of weakened vessels causes life-threatening events (heart attack, stroke or aneurysm). We defined an essential requirement for endothelial-secreted Tβ4 in mural cell differentiation for the development of stable vessels in the embryo. We are currently investigating the possibility that Tβ4 functions to maintain vascular stability throughout life and whether it may be protective in the context of vascular injury.
Phenotypic Switching in Aortic Vascular Smooth Muscle Cells