A total of seven driving pathways were included in this model (Figure 1) based on a manual curation of the macrophage literature: five pathways are relatively well-established M1 (IFNγ, TNFα, IL-1β) and M2 (IL-4, IL-10) stimuli, and the remaining two pathways (hypoxia, VEGF) were selected given their significance in PAD, which is our primary disease area of interest, as both factors are known to be critical drivers and regulators of PAD pathophysiology (Martinez and Gordon, 2014; Ouma et al., 2012). This evidence concerns the gene IL4 and peripheral arterial disease.