A 3D agent-based model of early AS (AS-ABM) was developed at UPF (http://dx.doi.org/10.1093/bioinformatics/btw551) and simulated the dynamic process of homeostatic disruption for the elimination of oxydized LDL (OXLDL), leading to the creation and accumulation of FC. Sensitivity analyses have revealed the relative importance of controlling the LDL oxidation rate, so as to avoid eventual atheroma. Yet, this oxidation rate is poorly documented and is per-se the result of dynamic processes that involve nitric oxide (NO) and tissue inflammation. Further model developments at UPF established new interactions among NO, EC inflammation and oxidative stress.

In order to relate these processes with measurable predictive biomarkers of cardiovascular events, the current agent rules and interactions need to be enriched with further network models. In particular, these development will target the mapping of the proteins from the LRP1 interactome that is involved in the evolution of prothrombotic smooth muscle cell. The project will combine the expertise of the Biomechanics & Mechanobiology group in computational systems biology, and the one of the Hospital de Sant Pau Research Institute in the exploration of the LRP1 interactome and predictive biomarkers.

Supervision: Jérôme Noailly, Vicenta Llorente Cortés (Sant Pau)