Assessing Endothelial Cell Function
Dysfunction of the endothelial cells lining the interior surface of blood vessels is thought to underpin atherosclerotic cardiovascular disease and is regarded as the bridge between risk factors and vascular disease. We have created novel computational models to study in vivo assessment methods of endothelial function.

Using Nektar1D we have created a novel computational model simulating arterial haemodynamics during flow-mediated dilation (FMD) (Am J Physiol, 2020), which is the most widely used in vivo test of endothelial function. The model was used to explain why FMD may be influenced by endothelium-independent factors, showing that FMD results are (i) partly masked by the vasoconstriction due to the change in transmural pressure and (ii) affected by physiological factors (i.e., arterial stiffness and arterial blood pressure) that are difficult to eliminate due to their multiple interactions (Am J Physiol, 2020). These results suggest that the current FMD test may not reflect the true endothelial cell response. Future work on controlling for these confounding factors may improve the relation between FMD and shear stress-stimulated release of endothelium-dependent relaxing factors.

We have also studied the possibility of assessing endothelial dysfunction by pulse wave analysis. Using Nektar1D we simulated pulse wave propagation in the larger systemic arteries of the mature rabbit (see figure above) (J Biomech, 2009). This model was used to elucidate haemodynamic mechanisms underlying changes in peripheral pulse waveforms observed in vivo after administering drugs that alter nitric oxide synthesis in the endothelial cells lining blood vessels, which is characteristic of endothelial dysfunction. According to our model, these changes can be explained by single or combined alterations of blood viscosity, peripheral resistance and compliance, and the elasticity of conduit arteries.

Our computational models can help elucidate the mechanisms underlying in vivo experimental results by testing hypotheses that cannot be addressed in vivo for technical and physiological reasons, such as the inability to access to all the vessels of interest and isolate variables without compensatory effects of cardiovascular homeostatic reflexes.