Hypoxia inducible factor-1alpha and expression of vascular endothelial growth factor and its receptors in cerebral arteriovenous malformations.
BACKGROUND
Vascular endothelial growth factor (VEGF) and its tyrosine kinase family of receptors (VEGFR) (Flt-1, Flk-1, Flt-4) have been implicated in vascular angiogenesis and remodelling in cerebral arteriovenous malformations (CAVM). In this study, we investigate the role of hypoxia inducible factor-1 (HIF-1alpha) in CAVM and its relationship to VEGF and VEGFR.


METHODS
Surgical specimens from 26 patients undergoing CAVM resection were studied for HIF-1alpha , VEGF, Flt-1, Flk-1 and Flt-4. The mean age was 34.08 +/- 14.18 years. Twenty-one patients presented with intracerebral haemorrhage.


RESULTS
VEGF, Flt-1 and Flt-4 were expressed in all specimens. Flk-1 was expressed in 15 of 26 patients. HIF-1alpha was expressed in 15 of 26 patients. HIF-1alpha expression was significantly associated with VEGF, Flt-1 and Flk-1 expression (p < 0.05)


CONCLUSIONS
HIF-1alpha is expressed in human CAVM. The expression of HIF-1alpha is significantly related to VEGF and VEGFR expression, suggesting a possible role for its induction and role in maintaining angiogenesis and vascular remodelling.
Ng
Ivan
I
Section of Cerebrovascular Surgery, Department of Neurosurgery, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore. ivan_ng@nni.com.sg
Tan
Wan-Loo
WL
Ng
Puay-Yong
PY
Lim
Joyce
J
D000293:Adolescent; D000328:Adult; D016009:Chi-Square Distribution; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D040262:Receptors, Vascular Endothelial Growth Factor / Q000145:classification / Q000378:metabolism*; D013223:Statistics as Topic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor