title: Modelling the influence of endothelial heterogeneity on the progression of arterial disease: application to abdominal aortic aneurysm evolution.
abstract: We sophisticate a fluid-solid growth computational framework for modelling aneurysm evolution. A realistic structural model of the arterial wall is integrated into a patient-specific geometry of the vasculature. This enables physiologically representative distributions of haemodynamic stimuli, obtained from a rigid-wall computational fluid dynamics analysis, to be linked to growth and remodelling algorithms. Additionally, a quasistatic structural analysis quantifies the cyclic deformation of the arterial wall so that collagen growth and remodelling can be explicitly linked to the cyclic deformation of vascular cells. To simulate aneurysm evolution, degradation of elastin is driven by reductions in wall shear stress (WSS) below homeostatic thresholds. Given that the endothelium exhibits spatial and temporal heterogeneity, we propose a novel approach to define the homeostatic WSS thresholds: We allow them to be spatially and temporally heterogeneous. We illustrate the application of this novel fluid-solid growth framework to model abdominal aortic aneurysm (AAA) evolution and to examine how the influence of the definition of the WSS homeostatic threshold influences AAA progression. We conclude that improved understanding and modelling of the endothelial heterogeneity is important for modelling aneurysm evolution and, more generally, other vascular diseases where haemodynamic stimuli play an important role.
authors.affiliation: Systems Biology Doctoral Training Centre, University of Oxford, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Aparício
authors.forename: A
authors.initials: A
authors.lastname: Mandaltsi
authors.forename: J
authors.initials: J
authors.lastname: Boamah
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Selimovic
authors.forename: M
authors.initials: M
authors.lastname: Bratby
authors.forename: R
authors.initials: R
authors.lastname: Uberoi
authors.forename: Y
authors.initials: Y
authors.lastname: Ventikos
authors.forename: P N
authors.initials: PN
authors.lastname: Watton
mesh_terms: D001012:Aorta, Abdominal / Q000473:pathology / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000503:physiopathology; D003198:Computer Simulation; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008955:Models, Cardiovascular; D013314:Stress, Mechanical
keywords: abdominal aortic aneurysm; cyclic deformation; endothelial cell; fluid-solid growth; growth and remodelling; homeostasis; wall shear stress