Multiscale Computational Modeling of Vascular Adaptation: A Systems Biology Approach Using Agent-Based Models.

The widespread incidence of cardiovascular diseases and associated mortality and morbidity, along with the advent of powerful computational resources, have fostered an extensive research in computational modeling of vascular pathophysiology field and promoted models as a support for biomedical research. Given the multiscale nature of biological systems, the integration of phenomena at different spatial and temporal scales has emerged to be essential in capturing mechanobiological mechanisms underlying vascular adaptation processes. In this regard, agent-based models have demonstrated to successfully embed the systems biology principles and capture the emergent behavior of cellular systems under different pathophysiological conditions. Furthermore, through their modular structure, agent-based models are suitable to be integrated with continuum-based models within a multiscale framework that can link the molecular pathways to the cell and tissue levels. This can allow improving existing therapies and/or developing new therapeutic strategies. The present review examines the multiscale computational frameworks of vascular adaptation with an emphasis on the integration of agent-based approaches with continuum models to describe vascular pathophysiology in a systems biology perspective. The state-of-the-art highlights the current gaps and limitations in the field, thus shedding light on new areas to be explored that may become the future research focus. The inclusion of molecular intracellular pathways (e.g., genomics or proteomics) within the multiscale agent-based modeling frameworks will certainly provide a great contribution to the promising personalized medicine. Efforts will be also needed to address the challenges encountered for the verification, uncertainty quantification, calibration and validation of these multiscale frameworks.