CDT Postgraduate Studentship in Healthcare Innovation (RCUK Digital Economy Programme grant number EP/G036861/1)
Endothelial heterogeneity in the evolution of vascular disease.
Aneurysms (excessive, permanent and localised dilatations of the arterial wall) present low rupture occurrence, but very high mortality and morbidity rates, when they rupture. While there are surgical interventions available, they are risky, costly and their evaluation is currently based on insufficient criteria. There is therefore a clinical need to develop a risk-of-rupture assessment, which can model the predicted evolution of an aneurysm.
The endothelium, the first arterial wall layer exposed to hemodynamic forces, translates mechanical stimuli from blood flow into physiologically important messages within the wall, resulting in remodelling of the wall structure in order to return the mechanical environment, for example the wall shear stress (WSS), to homeostatic levels. Endothelial cells show spatially and temporally varying properties, responding to the unique needs of the underlying tissue and to pathophysiological stimuli.
Endothelial heterogeneity, for instance, in defining WSS homeostasis, hadn’t previously been introduced in models of vascular disease evolution. Concepts, such as a temporally adaptive and spatially heterogeneous WSS homeostasis, implemented in 3D models for aneurysm evolution, can be further employed to model arterial adaptation in response to clinical intervention with devices as well as improve the development of tissue engineered vascular constructs.