Another mechanism that contributes to the endothelial dysfunction in IH is the production of extracellular vesicles by red blood cells, and their pathogenetic mechanism involves decreased eNOS, increased Endothelin-1 (ET-1) production via the Erk1/2 pathway, and phosphorylation via the PI3K/AKT pathway (Figure 1 [32]. This evidence concerns the gene AKT1 and isolated hemihyperplasia.