Increased endothelial progenitor cells and vasculogenic factors in higher-staged arteriovenous malformations.

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.