In this cross-sectional study, we found that (1) CLI patients present with a unique transcriptomic profile that is different from IC patients and non-PAD control; (2) fibrosis pathways that highlight TGFβ collagen deposition and VEGF distinguish CLI from IC and non-PAD control using transcriptomic data and IPA; and (3) increased fibrosis could be identified in CLI patients, validating the data we identified from the transcriptomic analysis (Figure 7). This evidence concerns the gene VEGFA and peripheral arterial disease.