title: Low shear stress‑induced autophagy alleviates cell apoptosis in HUVECs.
abstract: Low shear stress (LSS) is a well‑established risk factor resulting in endothelial apoptosis and atherosclerosis. Autophagy has been reported to be involved in the development of atherosclerosis. However, whether autophagy participates in LSS‑induced atherosclerosis remains unclear. The effect of autophagy and its association with apoptosis, in the development of atherosclerosis, remains controversial. Therefore, in the present study, the level and role of autophagy in human umbilical vein endothelial cells (HUVECs) exposed to LSS was examined. The results revealed that LSS increased the formation of autophagosomes and MAP1 light chain 3‑like protein (LC3) puncta (as demonstrated by transmission electron microscopy and immunofluorescence), and the protein levels of Beclin‑1 and LC3II decreased the expression of p62 [as revealed by western blot analysis (WB)]. Furthermore, the level of p62 decreased when autophagy was induced by rapamycin, and increased when autophagy was inhibited by chloroquine (CQ), which indicated that LSS may serve an important role in inducing autophagy flux. In addition, it was observed that HUVECs treated with LSS underwent apoptotic death, by monitoring the rate of apoptosis and the expression of apoptosis regulator BAX (Bax) and apoptosis regulator Bcl‑2 (Bcl‑2) (by flow cytometry and WB) and the LSS‑induced apoptosis in HUVECs, that was significantly alleviated by pretreatment with rapamycin, partially via a decrease in the level of Bax and an increase in the level of Bcl‑2. Pretreatment of HUVECs with CQ markedly increased LSS‑induced apoptosis, which was associated with an increased expression of Bax and a decreased expression of Bcl‑2. In conclusion, the results of the present study indicate that LSS increases the level of autophagy, which may be through a Bcl‑2/Beclin‑1‑dependent mechanism, which serves a protective role against LSS‑induced apoptosis.
authors.affiliation: Cardiovascular Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Dong
authors.affiliation: Cardiovascular Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Cardiovascular Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Yu
authors.affiliation: Cardiovascular Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Yu
authors.affiliation: Cardiovascular Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Qu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D000071186:Beclin-1 / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002738:Chloroquine / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D013314:Stress, Mechanical; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D051028:bcl-2-Associated X Protein; D002738:Chloroquine; D020123:Sirolimus