title: A novel chemo-mechano-biological model of arterial tissue growth and remodelling.
abstract: Arterial growth and remodelling (G&R) is mediated by vascular cells in response to their chemical and mechanical environment. To date, mechanical and biochemical stimuli tend to be modelled separately, however this ignores their complex interplay. Here, we present a novel mathematical model of arterial chemo-mechano-biology. We illustrate its application to the development of an inflammatory aneurysm in the descending human aorta. The arterial wall is modelled as a bilayer cylindrical non-linear elastic membrane, which is internally pressurised and axially stretched. The medial degradation that accompanies aneurysm development is driven by an inflammatory response. Collagen remodelling is simulated by adaption of the natural reference configuration of constituents; growth is simulated by changes in normalised mass-densities. We account for the distribution of attachment stretches that collagen fibres are configured to the matrix and, innovatively, allow this distribution to remodel. This enables the changing functional role of the adventitia to be simulated. Fibroblast-mediated collagen growth is represented using a biochemical pathway model: a system of coupled non-linear ODEs governs the evolution of fibroblast properties and levels of key biomolecules under the regulation of Transforming Growth Factor (TGF)-β, a key promoter of matrix deposition. Given physiologically realistic targets, different modes of aneurysm development can be captured, while the predicted evolution of biochemical variables is qualitatively consistent with trends observed experimentally. Interestingly, we observe that increasing the levels of collagen-promoting TGF-β results in arrest of aneurysm growth, which seems to be consistent with experimental evidence. We conclude that this novel Chemo-Mechano-Biological (CMB) mathematical model has the potential to provide new mechanobiological insight into vascular disease progression and therapy.
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK. Electronic address: pedro.aparicio@eng.ox.ac.uk.
authors.forename: Pedro
authors.initials: P
authors.lastname: Aparício
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK. Electronic address: mark.thompson@eng.ox.ac.uk.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Thompson
authors.affiliation: Department of Computer science, University of Sheffield, Sheffield, UK; INSIGNEO Institute for in silico Medicine, University of Sheffield, Sheffield, UK. Electronic address: p.watton@sheffield.ac.uk.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Watton
mesh_terms: D001158:Arteries / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D055595:Mechanical Phenomena; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D003094:Collagen
keywords: Aneurysm; Collagen; Fibroblast; Mathematical model; Mechanobiology; Remodelling; TGF-beta