title: Correlation of different NADPH oxidase homologues with late endothelial progenitor cell senescence induced by angiotensin II: effect of telmisartan.
abstract: OBJECTIVE
  Involvement of different NADPH oxidase (NOX) homologues in late endothelial progenitor cell (EPC) senescence induced by angiotensin II (Ang II) remains rarely studied systemically. The goal of our study was to determine NOX homologues which are correlated with late EPCs senescence induced by Ang II. The inhibitory effect of telmisartan was also studied.
  
  
  METHODS
  Late EPCs were obtained from mononuclear cells isolated from peripheral venous blood. Stimulated by Ang II with telmisartan (Tel) or VAS2870 pretreatment or siRNA prior silencing, NOX was detected by RT-PCR and Western blot. Cell senescence was measured by the acidic β-galactosidase activity assay and cell cycle analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometer based on DCFH-DA.
  
  
  RESULTS
  A bi-phasic change existed in NOX level after Ang II stimulation. Translocated NOX5 was correlated with early and rapid ROS production, but it contributed little to EPCs senescence. NOX2 and NOX4 were correlated with the late and slow phase and contributed greatly to EPCs senescence. There were no significant changes in NOX1 or NOX3. Telmisartan effectively depressed NOX change and delayed late EPCs senescence.
  
  
  CONCLUSIONS
  Ang II accelerates late EPCs senescence mainly via increased ROS originating from NOX2 and NOX4 up-regulation or translocated NOX5. Telmisartan effectively inhibited that cascade reaction and delayed EPCs senescence.
authors.affiliation: Department of Cardiology, the Affiliated Hangzhou Hospital, Nanjing Medical University, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Ningfu
authors.initials: N
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology*; D000077333:Telmisartan; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D000804:Angiotensin II; D019255:NADPH Oxidases; D000077333:Telmisartan