A multiscale computational model of arterial growth and remodeling including Notch signaling.
Biomech Model Mechanobiol
; 22(5): 1569-1588, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37024602
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hipertensión
/
Músculo Liso Vascular
Tipo de estudio:
Guideline
/
Prognostic_studies
/
Qualitative_research
Límite:
Humans
Idioma:
En
Revista:
Biomech Model Mechanobiol
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Países Bajos