title: Increased endothelial progenitor cells and vasculogenic factors in higher-staged arteriovenous malformations.
abstract: ACKGROUND:: Arteriovenous malformations cause significant morbidity, primarily because they expand over time and recur after treatment. The authors hypothesized that neovascularization might contribute to arteriovenous malformation progression.
  
  
  METHODS
  Arteriovenous malformation tissue was collected prospectively from 12 patients after resection. Schobinger stage was determined by clinical history. Neovascularization in stage II lesions (n=7) was compared with stage III arteriovenous malformations (n=5) that had progressed. Specimens were analyzed using immunohistochemistry for CD31, Ki67, and CD34/CD133. Quantitative real-time reverse-transcriptase polymerase chain reaction was used to determine mRNA expression of factors that recruit endothelial progenitor cells: vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), and hypoxia-inducible factor-1α (HIF-1α). VEGF receptors (VEGFR1, VEGFR2, neuropilin 1, and neuropilin 2) also were quantified using quantitative real-time reverse-transcriptase polymerase chain reaction.
  
  
  RESULTS
  Stage III arteriovenous malformations showed greater microvessel density (5.8 percent) than stage II lesions (1.3 percent) (p=0.004); no difference in proliferating endothelial cells was noted (p=0.67). CD133CD34 endothelial progenitor cells were elevated in stage III (0.53 percent) compared with stage II arteriovenous malformations (0.25 percent) (p=0.03). HIF-1α and SDF-1α were increased 7.6- and 7.9-fold in stage III compared with stage II lesions (1.7-fold and 3.3-fold), respectively (p=0.02). Neuropilin 1 and neuropilin 2 expression was greater in stage III (5.8-fold and 4.6-fold) than stage II arteriovenous malformations (3.0-fold and 2.4-fold) (p=0.03).
  
  
  CONCLUSIONS
  Higher-staged arteriovenous malformations exhibit increased expression of endothelial progenitor cells and factors that stimulate their recruitment. Neovascularization by vasculogenesis may be involved in progression of arteriovenous malformation.
authors.affiliation: Boston, Mass. From the Departments of Plastic and Oral Surgery and Surgery, Vascular Anomalies Center, Vascular Biology Program, Children's Hospital Boston, Harvard Medical School.
authors.forename: Lingge
authors.initials: L
authors.lastname: Lu
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Diane R
authors.initials: DR
authors.lastname: Bielenberg
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fishman
authors.forename: Arin K
authors.initials: AK
authors.lastname: Greene
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001165:Arteriovenous Malformations / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D002648:Child; D042783:Endothelial Cells / Q000166:cytology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013234:Stem Cells / Q000166:cytology / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A