Samenvatting
Blood vessels grow and remodel in response to mechanical stimuli. Many computational models capture this process phenomenologically, by assuming stress homeostasis, but this approach cannot unravel the underlying cellular mechanisms. Mechano-sensitive Notch signaling is well-known to be key in vascular development and homeostasis. Here, we present a multiscale framework coupling a constrained mixture model, capturing the mechanics and turnover of arterial constituents, to a cell-cell signaling model, describing Notch signaling dynamics among vascular smooth muscle cells (SMCs) as influenced by mechanical stimuli. Tissue turnover was regulated by both Notch activity, informed by in vitro data, and a phenomenological contribution, accounting for mechanisms other than Notch. This novel framework predicted changes in wall thickness and arterial composition in response to hypertension similar to previous in vivo data. The simulations suggested that Notch contributes to arterial growth in hypertension mainly by promoting SMC proliferation, while other mechanisms are needed to fully capture remodeling. The results also indicated that interventions to Notch, such as external Jagged ligands, can alter both the geometry and composition of hypertensive vessels, especially in the short term. Overall, our model enables a deeper analysis of the role of Notch and Notch interventions in arterial growth and remodeling and could be adopted to investigate therapeutic strategies and optimize vascular regeneration protocols.
Originele taal-2 | Engels |
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Pagina's (van-tot) | 1569-1588 |
Aantal pagina's | 20 |
Tijdschrift | Biomechanics and Modeling in Mechanobiology |
Volume | 22 |
Nummer van het tijdschrift | 5 |
DOI's | |
Status | Gepubliceerd - okt. 2023 |
Financiering
Financiers | Financiernummer |
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European Union’s Horizon Europe research and innovation programme | 846617 |
Vingerafdruk
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Data belonging to the publication "A multiscale computational model of arterial growth and remodeling including Notch signaling"
van Asten, J. G. M. (Ontwerper), Latorre, M. (Ontwerper), Karakaya, C. (Ontwerper), Baaijens, F. P. T. (Ontwerper), Sahlgren, C. M. (Ontwerper), Ristori, T. (Ontwerper), Humphrey, J. D. (Ontwerper) & Loerakker, S. (Ontwerper), 4TU.Centre for Research Data, 18 okt. 2023
DOI: 10.4121/22040729, https://data.4tu.nl/datasets/9fe0ab83-7577-4cc0-8fc1-ebc9e6df297a en nog één link, https://data.4tu.nl/datasets/9fe0ab83-7577-4cc0-8fc1-ebc9e6df297a/1 (minder tonen)
Dataset