Multiscale Modeling of Vascular Remodeling Induced by Wall Shear Stress

OBJECTIVE: Hemodynamics-induced low wall shear stress (WSS) is one of the critical reasons leading to vascular remodeling. However, the coupling effects of WSS and cellular kinetics have not been clearly modeled. The aim of this study was to establish a multiscale modeling approach to reveal the vascular remodeling behavior under the interaction between the macroscale of WSS loading and the microscale of cell evolution. METHODS: Computational fluid dynamics (CFD) method and agent-based model (ABM), which have significantly different characteristics in temporal and spatial scales, were adopted to establish the multiscale model. The CFD method is for the second/organ scale, and the ABM is for the month/cell scale. The CFD method was used to simulate blood flow in a vessel and obtain the WSS in a vessel cross-section. The simulations of the smooth muscle cell (SMC) proliferation/apoptosis and extracellular matrix (ECM) generation/degradation in a vessel cross-section were performed by using ABM. During the simulation of the vascular remodeling procedure, the damage index of the SMC and ECM was defined as deviation from the obtained WSS. The damage index decreased gradually to mimic the recovery of WSS-induced vessel damage. RESULTS: (1) The significant wall thickening region was consistent with the low WSS region. (2) There was no evident change of wall thickness in the normal WSS region. (3) When the damage index approached to 0, the amount and distribution of SMCs and ECM achieved a stable state, and the vessel reached vascular homeostasis. CONCLUSION: The established multiscale model can be used to simulate the vascular remodeling behavior over time under various WSS conditions.