A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

Coccarelli, A., Edwards, D. H., Aggarwal, A. , Nithiarasu, P. and Parthimos, D. (2018) A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics. Journal of the Royal Society: Interface, 15(139), 20170732. (doi: 10.1098/rsif.2017.0732) (PMID:29436507) (PMCID:PMC5832725)

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Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; and ryanodine, a diterpenoid that modulates Ca2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca2+ dynamics. Cytosolic Ca2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone.

Item Type:Articles
Additional Information:The authors acknowledge the financial support provided by the Sêr Cymru National Research Network in Advanced Engineering and Materials and the EPSRC (grant number: EP/P018912/1).
Glasgow Author(s) Enlighten ID:Aggarwal, Dr Ankush
Authors: Coccarelli, A., Edwards, D. H., Aggarwal, A., Nithiarasu, P., and Parthimos, D.
College/School:College of Science and Engineering > School of Engineering > Infrastructure and Environment
Journal Name:Journal of the Royal Society: Interface
Publisher:The Royal Society
ISSN (Online):1742-5662
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of the Royal Society: Interface 15:20170732.
Publisher Policy:Reproduced under a Creative Commons License

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