Modeling of the early stage of atherosclerosis with emphasis on the regulation of the endothelial permeability. (7th July 2020)

• Record Type: Journal Article
• Authors: Silva, Telma; Jäger, Willi; Neuss-Radu, Maria; Sequeira, Adélia
• Is Part Of: Journal of theoretical biology. Volume 496(2020)
• Publication Date: 2020-07-07
• Subjects: Mathematical modeling and simulations -- Early inflammation -- Atherosclerosis -- Endothelial permeability -- Low-density-lipoprotein dynamics -- Immune cells dynamics; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2020.110229
• Languages: English
• ISSNs: 0022-5193

Abstract

Highlights: Endothelial dysfunction plays a fundamental role in the atherosclerotic disease. In this model, the endothelium is a separate compartment with associated variables. Coupling of the inflammatory processes with the fluid dynamics-mechanical processes. Model simulations quantify influence of various factors on endothelial permeability. Abstract: In this paper, we develop a mathematical model for the early stage of atherosclerosis, as a chronic inflammatory disease. It includes also processes that are relevant for the "thickening" of the vessel walls, and prepares a more complete model including also the later stages of atherosclerosis. The model consists of partial differential equations: Navier-Stokes equations modeling blood flow, Biot equations modeling the fluid flow inside the poroelastic vessel wall, and convection/chemotaxis-reaction-diffusion equations modeling transport, signaling and interaction processes initiating inflammation and atherosclerosis. The main innovations of this model are: a) quantifying the endothelial permeability to low-density-lipoproteins (LDL) and to the monocytes as a function of WSS, cytokines and LDL on the endothelial surface; b) transport of monocytes on the endothelial surface, mimicking the monocytes adhesion and rolling; c) the monocytes influx in the lumen, as a function of factor increasing monocytopoiesis; d) coupling between Navier-Stokes system, Biot system and convection/chemotaxis-reaction-diffusion equations. Numerical simulations of a simplified model were performed in an idealized two-dimensional geometry in order to investigate the dynamics of endothelial permeability, and the growth and spread of immune cells populations and their dependence in particular on low-density-lipoprotein and wall-shear stress.