title: Angiotensin-(1-7) treatment ameliorates angiotensin II-induced apoptosis of human umbilical vein endothelial cells.
abstract: Angiotensin (Ang)-(1-7), a metabolite of AngI and AngII, is a counter-regulatory mediator of AngII. In the present study, we investigated the effects of Ang-(1-7) on AngII-induced apoptosis in human umbilical vein endothelial cells (HUVEC). To this end, HUVEC were pretreated with 10(-9), 10(-8), 10(-7) or 10(-6) mol/L Ang-(1-7) at for 30 min before being stimulated with 10(-6) mol/L Ang-II for another 24 h. Acridine orange/ethidium bromide and propidium iodide staining were used to analyse the effects of Ang-(1-7) on AngII-induced apoptosis. Alone, 10(-6) mol/L Ang-(1-7) had no effect on the apoptosis of HUVEC following exposure of cells for 30 min, whereas AngII (10(-6) mol/L, 24 h) significantly enhanced the number of apoptotic cells (P < 0.01). The AngII-induced apoptosis of HUVEC was suppressed by 10(-9)-10(-6) mol/L Ang-(1-7). The anti-apoptotic effects of Ang-(1-7) were almost completely abolished by A-779 (10(-6) mol/L, 30 min), a specific Mas receptor antagonist. In addition, Ang-(1-7) inhibited AngII-induced accumulation of cleaved caspase 3 and enhanced the expression of the anti-apoptotic factor Bcl-2 at both the mRNA and protein levels. Angiotensin II upregulated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which is involved in endothelial apoptosis, at both the mRNA and protein levels. This effect was blocked by Ang-(1-7) in a concentration-dependent manner, although A-779 almost completely reversed Ang-(1-7)-mediated inhibition of AngII-induced upregulation of LOX-1. Silencing of LOX-1 using short interference RNA enhanced the protective effects of Ang-(1-7) against AngII-induced apoptosis in HUVEC. Together, the results suggest that Ang-(1-7) ameliorates AngII-induced apoptosis of HUVEC at least in part by suppressing LOX-1 expression.
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Yang
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Bian
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Zhang
authors.forename: Fen
authors.initials: F
authors.lastname: Gao
authors.forename: Chuan-Shi
authors.initials: CS
authors.lastname: Xiao
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Zhang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Yang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C495137:OLR1 protein, human; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051127:Scavenger Receptors, Class E; D000804:Angiotensin II; D000803:Angiotensin I; D053148:Caspase 3; C118790:angiotensin I (1-7)