Given that eNOS-NO is well known to oppose vascular inflammation, adhesion of platelets and leukocytes, and proliferation and aging of ECs [53, 54], we hypothesize that the above conditions have an especially detrimental effect on collateral ECs—similar to the elevated proliferation of collateral ECs, increased tortuosity, and eventual collateral rarefaction that occurs with aging and chronic risk factor presence [29–31] which, themselves, cause increased vascular oxidative stress, inflammation, and endothelial dysfunction [6, 53, 54, 85]. This evidence concerns the gene NOS3 and endothelial dysfunction.