title: Does hypoxia play a role in infantile hemangioma?
abstract: Infantile hemangioma (IH), the most common tumor of infancy, is characterized by rapid growth during infancy, followed by spontaneous involution over 5-10 years. Certain clinical observations have led to the suggestion that IH is triggered and maintained by hypoxia. We review the literature on the possible role of hypoxia in the etiology of IH, in particular, (1) the role of hypoxia inducible factor-1α (HIF-1α) and its downstream targets including GLUT-1 and VEGF; (2) the pathophysiological link between IH and retinopathy of prematurity; (3) hypoxic events in the early life including placental insufficiency, pre-eclampsia and low birthweight that have the potential to promote hypoxic stress; and (4) the evidence supporting the development of IH independent of HIF-1α. We also discuss these observations in the context of recent evidence of the crucial role of stem cells and the cytokines niche that governs their proliferation and inevitable differentiation, offering novel insights into the biology of IH. We propose that various triggers may simultaneously up-regulate HIF-1α, which is downstream of the renin-angiotensin system, specifically angiotensin II, which promotes production of HIF-1α. These developments shed light to the understanding of this enigmatic condition.
authors.affiliation: Gillies McIndoe Research Institute, Newtown, Wellington, New Zealand.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Jong
authors.affiliation: Gillies McIndoe Research Institute, Newtown, Wellington, New Zealand.
authors.forename: Tinte
authors.initials: T
authors.lastname: Itinteang
authors.affiliation: Centre for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand.
authors.forename: Aaron H J
authors.initials: AH
authors.lastname: Withers
authors.affiliation: Gillies McIndoe Research Institute, Newtown, Wellington, New Zealand.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Davis
authors.affiliation: Gillies McIndoe Research Institute, Newtown, Wellington, New Zealand. swee.tan@gmri.org.nz.|Centre for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand. swee.tan@gmri.org.nz.
authors.forename: Swee T
authors.initials: ST
authors.lastname: Tan
mesh_terms: D000804:Angiotensin II / Q000235:genetics; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006391:Hemangioma / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D010927:Placental Insufficiency / Q000473:pathology; D011225:Pre-Eclampsia / Q000473:pathology; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000502:physiology*; D012178:Retinopathy of Prematurity / Q000209:etiology; D013234:Stem Cells / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II
keywords: Hypoxia-inducible factor-alpha; Infantile hemangioma; Renin–angiotensin system; Retinopathy; Stem cells