title: Attenuation of exogenous angiotensin II stress-induced damage and apoptosis             in human vascular endothelial cells via microRNA-155 expression.
abstract: Numerous studies have indicated that cells and tissues have means of blocking             their response to continuous stress signals to protect themselves from damage.             Overexpression of angiotensin II (Ang II) in the renin-angiotensin system can             cause vascular endothelial damage, but the mechanism of adjustment of the dynamic             equilibrium remains unclear. In this study, we investigated whether microRNA-155             (miR-155) can suppress continuous Ang II stress signals that would otherwise cause             vascular endothelial damage. We isolated and cultured human umbilical vein endothelial             cells (HUVECs) and transfected one group of these with a mature miR-155 expression             plasmid. Quantitative real-time PCR (qRT-PCR) and western blotting showed Ang II             type 1 receptor expression to be decreased in miR-155-transfected HUVECs compared             with untransfected cells. The MTT proliferation assay revealed that exogenous             Ang II suppressed proliferation of HUVECs in a concentration-dependent manner.             When HUVECs were cultured in medium containing Ang II at the half maximal inhibitory             concentration (68.94 ng/µl) for 24 h, qRT-PCR and western blotting showed that             expression of the apoptosis inhibitor Bcl-2 in the HUVEC-Ang II group was markedly             lower than that in controls, but apoptosis-promoting factors (Bax, cytochrome c,             caspases-9 and -3) were not. Co-immunoprecipitation western blotting and immunofluorescence             staining showed that exogenous Ang II increased the phosphorylation and activation             of extracellular signal related kinase (ERK)1/2. Exogenous Ang II also influenced             HUVEC migration and capillary tubule formation in vitro. However, after transfection             of HUVECs with miR-155 under the same conditions, expression of apoptosis-promoting             factors and ERK1/2 phosphorylation were reduced significantly and HUVEC migration             and capillary tubule formation were restored to some extent. Thus, miR-155 attenuated             the effect of exogenous Ang II-induced ERK1/2 activation to reduce HUVEC damage             and apoptosis. Moreover, miR-155 maintained HUVEC migration and capillary tubule             formation in vitro.
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, PR China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.forename: Dingzhu
authors.initials: D
authors.lastname: Shen
authors.forename: Sanli
authors.initials: S
authors.lastname: Xing
authors.forename: Jiulin
authors.initials: J
authors.lastname: Chen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Beiling
authors.initials: B
authors.lastname: Wu
authors.forename: Huiying
authors.initials: H
authors.lastname: Chi
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhao
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liang
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002196:Capillaries / Q000378:metabolism; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D013312:Stress, Physiological; D014162:Transfection
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D048052:Mitogen-Activated Protein Kinase 3