Hypoxia-inducible factor (HIF)–mediated effects of the hypoxic niche in bone cancer

Knowles, Helen J.

doi:10.1016/b978-0-12-821666-8.00028-1

Cited by 2 publications

(3 citation statements)

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“…54 In mouse cortical tissue, HIF-1a expression in the brain peaks at 6-12 hours and normalizes within $3 weeks. 11 Iron -due to its constituent role in HIF stabilization, via prolyl hydroxylase activity 13 -can influence the coordination of HIF-mediated responses designed to maintain O 2 delivery. 55 However, because iron deficiency commonly occurs with sojourn to high altitude, 16,17,55,56 the responsiveness at which downstream HIF responses are stimulated might be influenced by the individuals' prevailing iron status.…”

Section: Discussionmentioning

confidence: 99%

“…vascular endothelial growth factor, erythropoietin (EPO)] in the brain, that increase cerebral microvascular density and hematocrit (Hct) within 3 weeks. 12 Similarly, inactivation of prolyl-hydroxylase [the site whereby iron acts to influence the stability of HIF] 13 leads to HIF expression, neurovascular angiogenesis and pericyte proliferation in mice. 14 Finally, cerebral astrocytes (but not cerebral neurons) exposed to extreme hypoxia and desferrioxamine (DFO; iron chelator) showed an increase in EPO expression via HIF-2α up-regulation.…”

Section: Introductionmentioning

confidence: 99%

“…Iron and iron-chelation are typically utilized to down-and up-regulate HIF expression -due to iron's constituent role in HIF stabilization, via prolyl hydroxylase activity 13 -which have repeatedly demonstrated notable implications in pulmonary, [16][17][18][19][20][21][22][23][24] and peripheral vascular regulation. 25 However, limited data exists with respect to the cerebral vasculature.…”

Section: Introductionmentioning

confidence: 99%

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Manipulation of iron status on cerebral blood flow at high altitude in lowlanders and adapted highlanders

Patrician

Willie

Hoiland

et al. 2023

J Cereb Blood Flow Metab

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Cerebral blood flow (CBF) increases during hypoxia to counteract the reduction in arterial oxygen content. The onset of tissue hypoxemia coincides with the stabilization of hypoxia-inducible factor (HIF) and transcription of downstream HIF-mediated processes. It has yet to be determined, whether HIF down- or upregulation can modulate hypoxic vasodilation of the cerebral vasculature. Therefore, we examined whether: 1) CBF would increase with iron depletion (via chelation) and decrease with repletion (via iron infusion) at high-altitude, and 2) explore whether genotypic advantages of highlanders extend to HIF-mediated regulation of CBF. In a double-blinded and block-randomized design, CBF was assessed in 82 healthy participants (38 lowlanders, 20 Sherpas and 24 Andeans), before and after the infusion of either: iron(III)-hydroxide sucrose, desferrioxamine or saline. Across both lowlanders and highlanders, baseline iron levels contributed to the variability in cerebral hypoxic reactivity at high altitude (R2 = 0.174, P < 0.001). At 5,050 m, CBF in lowlanders and Sherpa were unaltered by desferrioxamine or iron. At 4,300 m, iron infusion led to 4 ± 10% reduction in CBF (main effect of time p = 0.043) in lowlanders and Andeans. Iron status may provide a novel, albeit subtle, influence on CBF that is potentially dependent on the severity and length-of-stay at high altitude.

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