Computational investigation of the role of low-density lipoprotein and oxygen transport in atherosclerotic arteries

Atherosclerosis is one of the major causes of death and morbidity in Western countries. It is a chronic inflammatory disease of the arterial wall consisting of the buildup of fatty plaques resulting in narrowing the vessel lumen. Among the multiple biological, systemic, and biomechanical factors influencing the initiation and progression of atherosclerotic disease, a high plasma level of low-density lipoprotein (LDL) is considered to be the main cause of atherosclerotic lesion development. Indeed, LDL accumulation in the arterial intima has been recognized as a hallmark of early atherosclerosis. Moreover, altered hemodynamic forces acting at the vascular wall, for example, in the form of low and/or oscillatory wall shear stress (WSS), may induce endothelial dysfunction, with the establishment of pathologic dynamics potentially leading to increased lipid wall uptake and atherogenesis. Previous clinical evidence has shown that the general atherosclerotic scenario is characterized by the colocalization of luminal LDL polarization with luminal areas of hypoxia and low and/or oscillatory WSS, thus suggesting a role of mass transport in plaque formation and progression. Accordingly, the investigation of the atherogenic role of LDL and oxygen transport and, especially, its alteration due to disturbed flow patterns is of great interest. To this aim, personalized computational simulations are promising tools contributing to a deeper understanding of the phenomenon, allowing to solve the governing equations of fluid motion and mass transport in complex and patient-specific artery geometries. In particular, patient-specific computational fluid dynamics simulations may potentially clarify the interrelation among altered hemodynamics, LDL accumulation, hypoxia, and atherogenesis, thus addressing underlying mechanisms of localization of atherosclerotic plaques in predilection vascular sites, such as at the outer wall of bifurcations or vessel inner curvature. In this chapter, a review of computational models of mass transport of LDL and oxygen in different vascular segments, including coronary, carotid, femoral arteries, and aortas is proposed, with emphasis on the elucidation of their atherogenic role. Finally, future perspectives in this promising area are illustrated.