Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging: Potential Role for Hypoxia-Inducible Transcription Factor-1-Regulated Pathways.
Stroke
; 46(9): 2576-83, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26304864
ABSTRACT
BACKGROUND AND PURPOSE:
Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether hypoxia-inducible transcription factor-1 activation may be temporally correlated with vascular changes.METHODS:
We assessed cerebrovascular function (autoregulation, vasoreactivity, and neurovascular coupling) and serum concentrations of vascular endothelial growth factor and erythropoietin, as representative measures of hypoxia-inducible transcription factor-1 activation, during 6 hours of deferoxamine infusion in 24 young and 24 older healthy volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. Vascular endothelial growth factor and erythropoietin serum protein assays were conducted using the Meso Scale Discovery platform.RESULTS:
Deferoxamine elicited a strong age- and time-dependent increase in the plasma concentrations of erythropoietin and vascular endothelial growth factor, which persisted ≤3 hours post infusion (age effect P=0.04; treatment×time P<0.01). Deferoxamine infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment×time P<0.01; age P<0.01) and cerebral autoregulation (gain age×time×treatment P=0.04).CONCLUSIONS:
Deferoxamine infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum vascular endothelial growth factor and erythropoietin concentrations is supportive of shared hypoxia-inducible transcription factor-1-regulated pathways. Therefore, pharmacological activation of hypoxia-inducible transcription factor-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT013655104.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia por Quelação
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Circulação Cerebrovascular
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Eritropoetina
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Sideróforos
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Desferroxamina
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Fatores de Crescimento do Endotélio Vascular
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Fator 1 Induzível por Hipóxia
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Stroke
Ano de publicação:
2015
Tipo de documento:
Article