Combining Inflammation and Tissue Turnover in the Modeling of Atherosclerosis Development Following the Outside‐In Disease Approach

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autorschaft

Externe Organisationen

  • Karolinska Institutet
  • Medizinische Hochschule Hannover (MHH)
  • Royal Institute of Technology (KTH)
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Details

OriginalspracheEnglisch
Aufsatznummere70131
FachzeitschriftInternational Journal for Numerical Methods in Biomedical Engineering
Jahrgang41
Ausgabenummer12
PublikationsstatusVeröffentlicht - 17 Dez. 2025

Abstract

Atherosclerosis remains the leading cause of cardiovascular morbidity worldwide. However, its onset and progression are still
difficult to predict, and it remains unclear why certain arterial segments develop lesions while others remain unaffected. Recent
findings highlight a prominent role of the vasa vasorum (VV)—the small blood vessels embedded within the walls of larger ar-
teries—in driving disease development through an outside-in mechanism. In this view, perfusion deficits caused by vascular dys-
function may trigger chronic inflammation and promote plaque formation. To investigate this mechanism, we propose a novel
multi-field model that combines tissue turnover, inflammation, and kinematics-based tissue growth. Perfusion is governed by
a diffusion–reaction equation and accounts for VV dysfunction in supplying the outer arterial layers. Inflammation is captured
through a phase-field representation that tracks the evolving interface between non-inflamed and inflamed tissue. A multiplica-
tive decomposition of the deformation gradient then combines the inflammation-driven swelling and the homeostasis-driven
tissue turnover, which itself is regulated by mechanical stress. The numerical implementation is realized using the standard fi-
nite element method. We assess model performance and plausibility through well-designed numerical case studies. The acquired
simulation results highlight the coupled interaction among transport of blood-borne factors, inflammation, and mechanics,
ultimately emphasizing how compromised VV can initiate a vicious cycle of ischemia, inflammation, and plaque growth in
an outside-in fashion. In addition, we show how a moderate increase in blood pressure may result in a progressive increase in
peak stress within atherosclerotic plaque tissue. Although our atherosclerosis model yields plausible predictions and allows deep
insights into the interaction of mechanics, inflammation and tissue turnover, it is based on multiple modeling approximations,
assumptions that would need sound validation in the future.

ASJC Scopus Sachgebiete

Zitieren

Combining Inflammation and Tissue Turnover in the Modeling of Atherosclerosis Development Following the Outside‐In Disease Approach. / Soleimani, Meisam; Pourbandari, Danial; Chemaly, Melody et al.
in: International Journal for Numerical Methods in Biomedical Engineering, Jahrgang 41, Nr. 12, e70131, 17.12.2025.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

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author = "Meisam Soleimani and Danial Pourbandari and Melody Chemaly and Philipp Junker and Axel Haverich and Peter Wriggers and Gasser, {T. Christian}",
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T1 - Combining Inflammation and Tissue Turnover in the Modeling of Atherosclerosis Development Following the Outside‐In Disease Approach

AU - Soleimani, Meisam

AU - Pourbandari, Danial

AU - Chemaly, Melody

AU - Junker, Philipp

AU - Haverich, Axel

AU - Wriggers, Peter

AU - Gasser, T. Christian

N1 - Publisher Copyright: © 2025 John Wiley & Sons Ltd.

PY - 2025/12/17

Y1 - 2025/12/17

N2 - Atherosclerosis remains the leading cause of cardiovascular morbidity worldwide. However, its onset and progression are stilldifficult to predict, and it remains unclear why certain arterial segments develop lesions while others remain unaffected. Recentfindings highlight a prominent role of the vasa vasorum (VV)—the small blood vessels embedded within the walls of larger ar-teries—in driving disease development through an outside-in mechanism. In this view, perfusion deficits caused by vascular dys-function may trigger chronic inflammation and promote plaque formation. To investigate this mechanism, we propose a novelmulti-field model that combines tissue turnover, inflammation, and kinematics-based tissue growth. Perfusion is governed bya diffusion–reaction equation and accounts for VV dysfunction in supplying the outer arterial layers. Inflammation is capturedthrough a phase-field representation that tracks the evolving interface between non-inflamed and inflamed tissue. A multiplica-tive decomposition of the deformation gradient then combines the inflammation-driven swelling and the homeostasis-driventissue turnover, which itself is regulated by mechanical stress. The numerical implementation is realized using the standard fi-nite element method. We assess model performance and plausibility through well-designed numerical case studies. The acquiredsimulation results highlight the coupled interaction among transport of blood-borne factors, inflammation, and mechanics,ultimately emphasizing how compromised VV can initiate a vicious cycle of ischemia, inflammation, and plaque growth inan outside-in fashion. In addition, we show how a moderate increase in blood pressure may result in a progressive increase inpeak stress within atherosclerotic plaque tissue. Although our atherosclerosis model yields plausible predictions and allows deepinsights into the interaction of mechanics, inflammation and tissue turnover, it is based on multiple modeling approximations,assumptions that would need sound validation in the future.

AB - Atherosclerosis remains the leading cause of cardiovascular morbidity worldwide. However, its onset and progression are stilldifficult to predict, and it remains unclear why certain arterial segments develop lesions while others remain unaffected. Recentfindings highlight a prominent role of the vasa vasorum (VV)—the small blood vessels embedded within the walls of larger ar-teries—in driving disease development through an outside-in mechanism. In this view, perfusion deficits caused by vascular dys-function may trigger chronic inflammation and promote plaque formation. To investigate this mechanism, we propose a novelmulti-field model that combines tissue turnover, inflammation, and kinematics-based tissue growth. Perfusion is governed bya diffusion–reaction equation and accounts for VV dysfunction in supplying the outer arterial layers. Inflammation is capturedthrough a phase-field representation that tracks the evolving interface between non-inflamed and inflamed tissue. A multiplica-tive decomposition of the deformation gradient then combines the inflammation-driven swelling and the homeostasis-driventissue turnover, which itself is regulated by mechanical stress. The numerical implementation is realized using the standard fi-nite element method. We assess model performance and plausibility through well-designed numerical case studies. The acquiredsimulation results highlight the coupled interaction among transport of blood-borne factors, inflammation, and mechanics,ultimately emphasizing how compromised VV can initiate a vicious cycle of ischemia, inflammation, and plaque growth inan outside-in fashion. In addition, we show how a moderate increase in blood pressure may result in a progressive increase inpeak stress within atherosclerotic plaque tissue. Although our atherosclerosis model yields plausible predictions and allows deepinsights into the interaction of mechanics, inflammation and tissue turnover, it is based on multiple modeling approximations,assumptions that would need sound validation in the future.

KW - atherosclerosis

KW - coupled analysis

KW - homeostasis

KW - inflammation

KW - vasa vasorum

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U2 - 10.1002/cnm.70131

DO - 10.1002/cnm.70131

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VL - 41

JO - International Journal for Numerical Methods in Biomedical Engineering

JF - International Journal for Numerical Methods in Biomedical Engineering

SN - 2040-7939

IS - 12

M1 - e70131

ER -

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