Computational analysis of the role of mechanosensitive Notch signaling in arterial adaptation to hypertension

Jordy G M van Asten, Tommaso Ristori, David R Nolan, Caitríona Lally, Frank P T Baaijens, Cecilia M Sahlgren, Sandra Loerakker*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Arteries grow and remodel in response to mechanical stimuli. Hypertension, for example, results in arterial wall thickening. Cell-cell Notch signaling between vascular smooth muscle cells (VSMCs) is known to be involved in this process, but the underlying mechanisms are still unclear. Here, we investigated whether Notch mechanosensitivity to strain may regulate arterial thickening in hypertension. We developed a multiscale computational framework by coupling a finite element model of arterial mechanics, including residual stress, to an agent-based model of mechanosensitive Notch signaling, to predict VSMC phenotypes as an indicator of growth and remodeling. Our simulations revealed that the sensitivity of Notch to strain at mean blood pressure may be a key mediator of arterial thickening in hypertensive arteries. Further simulations showed that loss of residual stress can have synergistic effects with hypertension, and that changes in the expression of Notch receptors, but not Jagged ligands, may be used to control arterial growth and remodeling and to intensify or counteract hypertensive thickening. Overall, we identify Notch mechanosensitivity as a potential mediator of vascular adaptation, and we present a computational framework that can facilitate the testing of new therapeutic and regenerative strategies.

Original languageEnglish
Article number105325
Pages (from-to)105325
JournalJournal of the Mechanical Behavior of Biomedical Materials
Volume133
DOIs
Publication statusPublished - Sep 2022
MoE publication typeA1 Journal article-refereed

Keywords

  • Arteries
  • Humans
  • Hypertension
  • Jagged-1 Protein/genetics
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle/physiology

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