Role Of Endoplasmic Reticulum Stress In Aortic Endothelium Apoptosis Induced By Intermittent/Persistent Hypoxia

Background: Accumulated evidences show that hypoxia can induce endotheliumapoptosis, however the mechanism is still unknown. This study was designed to test thehypothesis whether the intermittent hypoxia and persistent hypoxia could induce ER stress,leading to endothelium apoptosis.Methods:248-week male SD rats were divided into three groups: NC group (exposed tonormoxia), IH group(exposed to intermittent hypoxia) and PH group(exposed to persistenthypoxia). TUNEL staining were performed to detect the aortic arch endothelium apoptosis,and immunohistochemistry (IHC) for BIP, CHOP and caspase12were performed to testprotein expression; Human umbilical vein endothelial cells (HUVECs) of the line ECV304were cultured(with or without TUDCA10mmol/L,100mmol/L) and divided into4groups:NC1group(exposed to20.8%O2for4hours), PH1group(exposed to5%O2for4hours),PH2group(exposed to5%O2for12hours) and IH1group(exposed to20.8%O2and5%O2alternatively for4hours). Annexin V-fluorescein-isothiocyanate/propidium iodide flowcytometry was used to assess apoptosis in each group, The expressions of GRP78, CHOPand caspase12were detected by real-time quantitative reverse-transcription PCR.Result: Intermittent hypoxia and persistent hypoxia could increase the rate of endotheliumapoptosis significantly compared with the controls (P<0.05), and concomitantly, theexpression of BIP, CHOP and caspase12was increased notably(P<0.05). The rate of endothelium apoptosis and the expression of BIP, CHOP and caspase12induced byintermittent hypoxia was slightly higher than that of persistent hypoxia(P<0.05). In the vitroexperiment, TUDCA significantly reduced apoptosis and the expressions of BIP, CHOP andcaspase12in the HUVECs (P<0.01).Conclusion: Hypoxia, especially the intermittent hypoxia, can induce endothelial cellsapoptosis through endoplasmic reticulum stress pathway, which can be attenuated byTUDCA.