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Support for the hypoxia theory in the pathogenesis of infantile haemangioma
Author(s) -
Janmohamed S. R.,
Brinkhuizen T.,
Hollander J. C.,
Madern G. C.,
Laat P. C.,
Steensel M. A.,
Oranje A. P.
Publication year - 2015
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.12557
Subject(s) - erasmus+ , medicine , library science , sociology , history , art history , computer science , the renaissance
Summary Background The pathogenesis of infantile haemangioma ( IH ) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia‐inducible factor ( HIF )1α. HIF 1α stimulates downstream transcription of target genes that enhance angiogenesis. Aim To identify possible involvement of hypoxia in the pathogenesis of IH , as hypoxia signalling constitutes a potential therapeutic target. Methods IH tissue samples collected during the period 1991–2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD ‐interacting protein family member 3 (BNIP3), carbon anhydrase (CA)‐IX, glucose transporter (GLUT)‐1, phosphorylated protein kinase B ( pAKT ), phosphorylated S6 protein ( pS 6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. Results Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT‐1, BNIP3, pAKT and VEGF were positive, CA‐IX was weakly positive, and HIF1α was negative. pS 6 was positive in 9/10 cases and negative in 1/10. Conclusions Several factors implicated in hypoxia‐induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.