A new correlation for inclusion of leaky junctions in macroscopic modeling of atherosclerotic lesion initiation

Abstract

Vascular endothelium cells are the main barriers between vessel wall and blood flow; they play an essential role in the progression of atherosclerosis. Various experimental and computational studies have been carried out to identify the pathways and mechanisms by which Low Density Lipoprotein (LDL) transfers through the endothelium cells. The most conventional hypothesis in LDL transfer is the presence of leaky junctions. Leaky junctions are large pores in endothelium cells associated with cell mitosis or apoptosis. Although some studies have microscopically modeled leaky junctions, none however have evaluated their effects in a macroscopic level modeling. In this study, a new approach is proposed to consider the presence of the leaky junction as the main pathway in LDL transport from the lumen into the arterial wall. LDL transport in macroscopic scale is simulated in a simplified axisymmetric model and Staverman filtration coefficient (SFC) is used as a measurement criterion for estimating the amount of leaky junctions. According to the results, decreasing SFC corresponds to decreasing the resistance of endothelium cells. In other words, an increase in the number of leaky junctions causes an increase in the LDL concentration inside the arterial wall. Additionally, a new correlation is presented for evaluating the fraction of leaky junctions in the endothelial cells by comparing the results of macroscopic and microscopic models. This correlation accredits each SFC to a specified fraction of leaky junction in the endothelial cells. Therefore, it can be used for the inclusion of leaky junctions in the macroscopic modeling without incorporating any of the complications that are raised by the microscopic modeling studies. This correlation has important implications in the modeling of the atherosclerosis lesions propagation.