In PAD patients, prolonged exposure to ischemia might turn on some epigenetic switch such as the LIN28/let-7 feedback loop that potently silences let-7 expression, so let-7 abundance is markedly reduced even in cell that has high HIF-1 level in response to hypoxic stimulus; as a result, AGO1 expression is less inhibited in hypoxia which leads to impaired VEGF desuppression and synthesis [84]. The gene discussed is HIF1A; the disease is peripheral arterial disease.