Personalized multiscale modeling of coronary plaque progression: the interaction between low-density-lipoprotein transport and cellular dynamics

Multiscale agent-based modeling has shown promise in elucidating the mechanobiological mechanisms underlying atherosclerotic plaque formation and progression. However, the integration of advanced models of low-density lipoprotein (LDL) transport in the lumen and across the endothelium with agent-based models (ABMs) of plaque growth remains underexplored. Furthermore, patient-specific applications are lacking. This study introduces a novel agent-based modeling framework for atherosclerosis, integrating hemodynamics and LDL transport in the lumen through computational fluid dynamics simulations, a three-pore model of trans-endothelial LDL migration, and an ABM of lipid and cellular dynamics. For the first time, the framework was applied to a patient-specific coronary artery and validated against 1-year follow-up data. Furthermore, it was used to explore potential plaque evolution over 5 years and under elevated LDL concentration. The calibrated model predicted the 1-year variation in wall area in two patient-specific coronary cross-sections with an error of less than 10%. Simulated scenarios indicated that variations in blood LDL concentrations can result in distinct plaque morphologies, from localized to diffuse patterns. This study provided an innovative, advanced multiscale model of atherosclerotic plaque formation and progression. As the first patient-specific application of a multiscale agent-based modeling framework for atherosclerosis with initial validation, this study underscored the potential of the approach for deciphering the mechanobiological pathways driving coronary plaque progression. The developed model provided valuable insights into how the interplay between LDL transport and hemodynamics influences arterial wall cellular dynamics in a patient-specific context.