Stem cells effectively alleviated endothelial dysfunction under hypoxic conditions by strengthening ATF6 and initiating a transcriptional program to restore ER homeostasis, induce BIP expression, promote protein chaperones and lipid synthesis, stimulate ER degradation, and enhance N-glycosylation of XBP1 by increasing the ER’s folding capacity, as well as increasing the expression of chaperones and proteins involved in ER-associated degradation (by ER degradation-enhancing α-mannosidase-like protein [EDEM]) and vesicular trafficking. Here, EDEM1 is linked to endothelial dysfunction.