Since PAD prevalence increases significantly with age, another possible explanation about PAD-related miR feature looks at the loss-of-function of HIF-1 transcription factor in aging endothelial cells; nuclear import of HIF-1α is decreased in aging GMECs compared to young GMECs, and this severely blunts the induction of HIF-1 target genes including VEGF and let-7 in hypoxia [58, 85]. This evidence concerns the gene HIF1A and peripheral arterial disease.