Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma

Mark E. Kleinman, Matthew R. Greives, Samara S. Churgin, Keith M. Blechman, Eric I. Chang, Daniel J. Ceradini, Oren M. Tepper, Geoffrey C. Gurtner

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

OBJECTIVE - The mechanism of neovascularization during the proliferative phase of infantile hemangioma is poorly understood. It is known that circulating bone marrow-derived endothelial progenitor cells (EPCs) form new blood vessels in ischemic tissues using mediators regulated by the transcription factor, HIF-1α. Mobilization of EPCs is enhanced by VEGF-A, matrix metalloproteinase (MMP)-9, and estrogen, whereas homing is secondary to localized expression of stromal cell-derived factor-1α (SDF-1α). We examined whether these mediators of EPC trafficking are upregulated during the proliferation of infantile hemangioma. METHODS AND RESULTS - Surgical specimens and blood samples were obtained from children with proliferating hemangioma and age-matched controls (n=10, each group). VEGF-A and MMP-9 levels were measured in blood, and tissue sections were analyzed for SDF-1α, MMP-9, VEGF-A, and HIF-1α. The role of estrogen as a modulator of hemangioma endothelial cell growth was also investigated. We found that all these mediators of EPC trafficking are elevated in blood and specimens from children with proliferating infantile hemangioma. In vitro, the combination of hypoxia and estrogen demonstrated a synergistic effect on hemangioma endothelial cell proliferation. CONCLUSIONS - These findings demonstrate that proliferating hemangiomas express known mediators of vasculogenesis and suggest that this process may play a role in the initiation or progression of this disease.

Original languageEnglish (US)
Pages (from-to)2664-2670
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume27
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Hemangioma
Stem Cells
Matrix Metalloproteinase 9
Vascular Endothelial Growth Factor A
Chemokine CXCL12
Estrogens
Endothelial Cells
Hypoxia
Blood Vessels
Disease Progression
Transcription Factors
Bone Marrow
Cell Proliferation
Endothelial Progenitor Cells
Growth

Keywords

  • Chemokines
  • Endothelial progenitor cells
  • Hemangioma
  • Hypoxia
  • Vasculogenesis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Kleinman, M. E., Greives, M. R., Churgin, S. S., Blechman, K. M., Chang, E. I., Ceradini, D. J., ... Gurtner, G. C. (2007). Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(12), 2664-2670. https://doi.org/10.1161/ATVBAHA.107.150284

Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma. / Kleinman, Mark E.; Greives, Matthew R.; Churgin, Samara S.; Blechman, Keith M.; Chang, Eric I.; Ceradini, Daniel J.; Tepper, Oren M.; Gurtner, Geoffrey C.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 27, No. 12, 12.2007, p. 2664-2670.

Research output: Contribution to journalArticle

Kleinman, Mark E. ; Greives, Matthew R. ; Churgin, Samara S. ; Blechman, Keith M. ; Chang, Eric I. ; Ceradini, Daniel J. ; Tepper, Oren M. ; Gurtner, Geoffrey C. / Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2007 ; Vol. 27, No. 12. pp. 2664-2670.
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AU - Chang, Eric I.

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AB - OBJECTIVE - The mechanism of neovascularization during the proliferative phase of infantile hemangioma is poorly understood. It is known that circulating bone marrow-derived endothelial progenitor cells (EPCs) form new blood vessels in ischemic tissues using mediators regulated by the transcription factor, HIF-1α. Mobilization of EPCs is enhanced by VEGF-A, matrix metalloproteinase (MMP)-9, and estrogen, whereas homing is secondary to localized expression of stromal cell-derived factor-1α (SDF-1α). We examined whether these mediators of EPC trafficking are upregulated during the proliferation of infantile hemangioma. METHODS AND RESULTS - Surgical specimens and blood samples were obtained from children with proliferating hemangioma and age-matched controls (n=10, each group). VEGF-A and MMP-9 levels were measured in blood, and tissue sections were analyzed for SDF-1α, MMP-9, VEGF-A, and HIF-1α. The role of estrogen as a modulator of hemangioma endothelial cell growth was also investigated. We found that all these mediators of EPC trafficking are elevated in blood and specimens from children with proliferating infantile hemangioma. In vitro, the combination of hypoxia and estrogen demonstrated a synergistic effect on hemangioma endothelial cell proliferation. CONCLUSIONS - These findings demonstrate that proliferating hemangiomas express known mediators of vasculogenesis and suggest that this process may play a role in the initiation or progression of this disease.

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