Effects of estrogen on the apoptosis of human umbilical vein endothelial cells / 医学研究生学报

ABSTRACT

Objective Recent researches find that endoplasmic reticulum is a new target for the treatment of cardiovascular disease and its stress response plays an important role in the hypertension-induced cardiovascular remodeling.The study built up the apoptosis model of endoplasmic reticulum stress ( ERS) in human umbilical vein endothelial cells ( HUVECs) and investigated the im-pact of 17β-estradiol ( E2) on the ERS apoptosis of HUVECs induced by tunicamycinand(TM)/dithiothreitol(DTT). Methods HUVECs incubated for 10 h in 10μmol/L TM or 8 h in 2 mmol/L DTT were the best concentration and time for ERS apoptosis.E2 of 10-8 mol/L was prominent in protecting ERS.According to the application of TM/DTT, E2, estrogen antagonists (ICI182, 780 and G15), there were 6 groupscontrol group, TM/DTT group, TM/DTT+E2 group, TM/DTT+E2 +G15 group, TM/DTT+E2 +ICI+G15 group.Western blot was applied to detect the expressions of biomarkers for ERS in-duced apoptosis (GRP78, cleaved caspase-12 and CHOP).Hochest staining was used to observe the changes of the apoptosis cell number. Results Compared with control group, the expressions of GRP78, caspase-12 and CHOP significantly increased(P<0.05).In comparison with TM group, the expressions of GRP78, caspase-12 and CHOP in TM+E2 group significantly decreased (6.80 ±1.07 vs 4.01 ±0.46, 1.54 ±0.32 vs 0.88 ±0.10, 1.91 ±0.37 vs 0.91 ± 0.02, P<0.05).In comparison with TM +E2 group, the CHOP expression in TM +E2 +ICI group increased(0.91 ±0.02 vs 0.96 ±0.02, P<0.05), and the expressions of GRP78 and caspase-12 in TM+E2 +G15 group increased(4.01 ±0.46 vs 5.25 ± 0.80, 0.88 ±0.10 vs 1.02 ±0.07, P<0.05), and the expressions of GRP78, caspase-12 and CHOP in TM+E2 +ICI+G15 group increased (P<0.05).Compared with DTT group, the expressions of GRP78 and CHOP in DTT+E2 group decreased (1.81 ± 0.08 vs 1.30 ±0.14, 1.00 ±0.13 vs 0.51 ±0.01, P<0.05).In comparison with DTT+E2 group, the expressions of GRP78 and CHOP in DTT+E2 +ICI group decreased(P <0.05), and the expression of GPR78 in DTT+E2 +G15 group increased(P<0.05), and the expressions of GRP78, caspase-12 and CHOP in DTT+E2 +ICI+G15 group increased(P<0.05).The change of the apop-tosis cell number observed by hochest staining was in consistence with the result of western blot. Conclusion E2 can protect human endothelial cells from ERS induced apoptosis caused by TM and DTT.Estrogen maintains homeostasis by regulating ERS estrogen re-ceptors, thereby protecting the cardiovascular system.