Hypoxia is a potent trigger of angiogenesis. Some studies have focused on clarifying how hypoxia affects tumor angiogenesis through tumor cell-derived EVs. Hsu et al. found that more exosomes were produced under hypoxic conditions than normoxic conditions by lung cancer cells. Tumor-derived exosomal miR-23a directly suppressed the expression of prolyl- hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of HIF-1α in ECs and increased angiogenesis . Tadokoro et al. reported that exosomes derived from leukemia cells under hypoxia are potent inducers of angiogenesis through transfer of miR-210 to ECs, downregulating the expression of receptor tyrosine kinase ligand Ephrin-A3 in HUVECs . Neutral Sphingomyelinase 2 (nSMase2) was shown to regulate exosomal miR-210 secretion by metastatic cancer cells .