Inflammatory factor transport drives macrophage aggregation in an in silico aneurysm inflammation model

Abstract

Inflammation plays an important role in the pathological remodelling and rupture of intracranial aneurysms. One of the challenges in predicting the prognosis of intracranial aneurysms lies in the variation of the inflammatory state in aneurysm tissues from patient to patient. The connection between aneurysm biophysical environment and inflammation is largely unexplored by predictive computational models. In this study, a computational model based on a positive feedback mechanism driven by paracrine signalling between monocytes, macrophages and soluble inflammatory factors was proposed. Based on this model, three inflammatory factor transport regimes characterized by the dominance of (i) diffusion, (ii) production, or (iii) removal that drove at distinctive inflammatory dynamics were identified. A dimensionless group, production-to-transport ratio, strongly correlated with the simulated macrophage count (R2=0.97). The theoretical model in this work was simplified, but it demonstrated that inflammatory factor transport could have a profound impact on the inflammation process. This study suggests that haemodynamics may indirectly influence the state of inflammation, beyond the well-documented mechanosensory response of the vascular endothelium, by modulating the transport conditions for inflammatory factors.