title: Enhanced endothelial progenitor cell angiogenic potency, present in early experimental renovascular hypertension, deteriorates with disease duration.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) augment neovascularization and repair of damaged tissues, but may undergo functional changes during exposure to cardiovascular risk factors. This study tested the hypothesis that early renovascular hypertension (RVH) modulates the temporal pattern of EPC function that deteriorates with disease duration.
  
  
  METHODS
  RVH was induced in domestic pigs by unilateral renal artery stenosis. EPCs were cultured after 3, 6, and 12 weeks of RVH or normal control to evaluate EPC function, growth factor, and homing receptor expression. Plasma renin activity (PRA), vascular endothelial growth factor (VEGF), and its soluble receptor-1 (sFlt-1) were measured in plasma. EPCs (10 × 10) isolated from 3-week RVH or from normal pigs were also injected into control kidneys (n = 6-7, each group), and 4 weeks later single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were evaluated. Microvascular density was studied ex vivo using microcomputed tomography.
  
  
  RESULTS
  Blood pressure peaked at 3 weeks and remained higher than normal throughout the study. Systemic PRA also peaked after 3 weeks of RVH and declined thereafter, whereas sFlt-1 showed a reciprocal pattern. In vivo, only RVH but not normal EPCs increased RBF, GFR, and microvascular density. RVH-EPCs showed in vitro enhanced proliferation, tube formation, VEGF, and homing receptor expression that peaked at 3 weeks, which were abolished by valsartan and returned to baseline levels after 12 weeks of RVH. EPC number remained unchanged throughout the study.
  
  
  CONCLUSIONS
  A transient enhancement of EPC function, mediated by angiotensin II, may contribute to compensatory vascular adaptation in early RVH, but is lost as hypertension persists.
authors.affiliation: Division of Nephrology and Hypertension bDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.forename: Victor H
authors.initials: VH
authors.lastname: Urbieta Caceres
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Favreau
authors.forename: James D
authors.initials: JD
authors.lastname: Krier
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D053687:Adult Stem Cells / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology*; D005919:Glomerular Filtration Rate; D006978:Hypertension, Renovascular / Q000473:pathology* / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic; D012079:Renal Circulation; D012083:Renin / Q000097:blood; D012307:Risk Factors; D034421:Sus scrofa; D013997:Time Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D040281:Vascular Endothelial Growth Factor Receptor-1; D012083:Renin