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

Alberto Coccarelli Orcid Logo, David Edwards Orcid Logo, Ankush Aggarwal Orcid Logo, Perumal Nithiarasu Orcid Logo, Dimitris Parthimos

Journal of The Royal Society Interface, Volume: 15, Issue: 139

Swansea University Authors: Alberto Coccarelli Orcid Logo, David Edwards Orcid Logo, Ankush Aggarwal Orcid Logo, Perumal Nithiarasu Orcid Logo

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DOI (Published version): 10.1098/rsif.2017.0732

Abstract

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 a...

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Published in: Journal of The Royal Society Interface
ISSN: 1742-5689 1742-5662
Published: 2018
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URI: https://cronfa.swan.ac.uk/Record/cronfa38180
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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 &#x3B1;1-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. 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spelling 2021-01-07T13:46:31.4070037 v2 38180 2018-01-18 A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics 06fd3332e5eb3cf4bb4e75a24f49149d 0000-0003-1511-9015 Alberto Coccarelli Alberto Coccarelli true false fdbc6d03c1a53150cbe4c6055e9f08c1 0000-0001-9691-4736 David Edwards David Edwards true false 33985d0c2586398180c197dc170d7d19 0000-0002-1755-8807 Ankush Aggarwal Ankush Aggarwal true false 3b28bf59358fc2b9bd9a46897dbfc92d 0000-0002-4901-2980 Perumal Nithiarasu Perumal Nithiarasu true false 2018-01-18 MECH 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. Journal Article Journal of The Royal Society Interface 15 139 1742-5689 1742-5662 media, layerCa2+ dynamics, smooth muscle, multiscale modelling 28 2 2018 2018-02-28 10.1098/rsif.2017.0732 COLLEGE NANME Mechanical Engineering COLLEGE CODE MECH Swansea University EPSRC, EP/P018912/1 RCUK, EP/P018912/1 2021-01-07T13:46:31.4070037 2018-01-18T12:19:48.3274806 Faculty of Science and Engineering School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Civil Engineering Alberto Coccarelli 0000-0003-1511-9015 1 David Edwards 0000-0001-9691-4736 2 Ankush Aggarwal 0000-0002-1755-8807 3 Perumal Nithiarasu 0000-0002-4901-2980 4 Dimitris Parthimos 5 0038180-09022018134317.pdf coccarelli2018(2)v2.pdf 2018-02-09T13:43:17.4270000 Output 1779017 application/pdf Version of Record true 2018-02-09T00:00:00.0000000 © 2018 The Authors. Published under the terms of the Creative Commons Attribution License 4.0. true eng http://creativecommons.org/licenses/by/4.0/
title A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
spellingShingle A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
Alberto Coccarelli
David Edwards
Ankush Aggarwal
Perumal Nithiarasu
title_short A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
title_full A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
title_fullStr A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
title_full_unstemmed A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
title_sort A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics
author_id_str_mv 06fd3332e5eb3cf4bb4e75a24f49149d
fdbc6d03c1a53150cbe4c6055e9f08c1
33985d0c2586398180c197dc170d7d19
3b28bf59358fc2b9bd9a46897dbfc92d
author_id_fullname_str_mv 06fd3332e5eb3cf4bb4e75a24f49149d_***_Alberto Coccarelli
fdbc6d03c1a53150cbe4c6055e9f08c1_***_David Edwards
33985d0c2586398180c197dc170d7d19_***_Ankush Aggarwal
3b28bf59358fc2b9bd9a46897dbfc92d_***_Perumal Nithiarasu
author Alberto Coccarelli
David Edwards
Ankush Aggarwal
Perumal Nithiarasu
author2 Alberto Coccarelli
David Edwards
Ankush Aggarwal
Perumal Nithiarasu
Dimitris Parthimos
format Journal article
container_title Journal of The Royal Society Interface
container_volume 15
container_issue 139
publishDate 2018
institution Swansea University
issn 1742-5689
1742-5662
doi_str_mv 10.1098/rsif.2017.0732
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Civil Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Civil Engineering
document_store_str 1
active_str 0
description 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.
published_date 2018-02-28T03:48:15Z
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