title: Aliskiren directly improves endothelial progenitor cell function from Type II diabetic patients.
abstract: BACKGROUND
  Endothelial progenitor cell (EPC) functions are impaired in the presence of diabetes mellitus. Aliskiren is a direct renin inhibitor, which is expected to modify proangiogenic cells. This study aimed to investigate whether and how aliskiren could improve the function of EPCs from patients with type II diabetes (T2DM).
  
  
  METHODS
  Endothelial progenitor cells fibronectin adhesion assay, chamber assay and in vitro tube formation assay were used to estimate the degree of EPC adhesion, migration and tube formation abilities. EPC protein and mRNA expressions were evaluated by Western blot and quantitative RT-PCR, respectively. EPC vascular endothelial growth factor (VEGF) and (pro)renin receptor ((P)RR) expression was knocked down by VEGF and (P)RR siRNA.
  
  
  RESULTS
  Aliskiren (0·1 or 10 μM) dose-dependently improved functions and increased both VEGF and stromal cell-derived factor-1α (SDF-1α) expression of EPCs from patients with T2DM or EPCs from healthy volunteers and treated with high glucose. Transfection with VEGF siRNA significantly reduced the aliskiren-induced SDF-1α expression. Furthermore, (P)RR siRNA transfection impaired the aliskiren-induced VEGF and SDF-1 expression.
  
  
  CONCLUSIONS
  The results show that aliskiren improved EPC function from patients with T2DM in a dose-dependent manner probably via the (P)RR and VEGF/SDF-1α-related mechanisms.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Chang
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tao-Cheng
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jia-Shiong
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Liang-Yu
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D005650:Fumarates; D007093:Imidazoles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013777:Tetrazoles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006830:Hydralazine; C446481:aliskiren; C437965:olmesartan; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: (pro)renin receptor; Aliskiren; endothelial progenitor cell; high glucose; stromal cell-derived factor-1α; vascular endothelial growth factor