Smart Group

+44 (0) 1865 282365
nicola.smart@dpag.ox.ac.uk

Development, homeostasis and regeneration of the cardiovascular system

Following myocardial infarction, intrinsic mechanisms are deployed to revascularise the ischaemic tissue. These partly recapitulate the mechanisms of embryonic coronary vessel development.

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

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. mesenhcymal EPDC

Epithelial to Mesenchymal Transition for Mobilisation of EPDCs and Regeneration

coronary vasculature

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. aorta WT

Phenotypic Switching in Aortic Vascular Smooth Muscle Cells

Our team

Nicola Smart

BHF Ian Fleming Fellow and Professor of Cardiovascular Science
Jacinta Kalisch-Smith

Oxford BHF CRE Basic Science Intermediate Transition Fellow
Andia Redpath

Postdoctoral Research Associate
Ian McCracken

MRC Transition Fellow
Andrew Robson

Visiting Postdoctoral Researcher
Olivia Jones

MSc(Res) Graduate student
Thomas Nicol

Postdoctoral Research Scientist