Other stressors closely linked to the preeclampsia may also act through the same pathways, for example, high levels of maternal endothelin (ET)-1 or elevated plasma concentrations of homocysteine.57, 58, 59 We found that ET-1 down-regulates MMP-14 and -15 expression in first trimester trophoblast cells,60 and both ET-1 and homocysteine induce ER stress in trophoblast and other cell types.61, 62 Therefore, the finding of ER stress–regulated MMP2 expression may provide an additional mechanistic explanation for the actions of ET-1 and homocysteine in the development of pregnancy complications. This evidence concerns the gene MMP2 and preeclampsia.