Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging
| العنوان: | Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging |
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| المؤلفون: | Lewis A. Lipsitz, Can Ozan Tan, Sarah LaRose, Raina N. Fichorova, Stanthia Ryan, Farzaneh A. Sorond, Andrew D. Monk |
| المصدر: | Stroke. 46:2576-2583 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adult, Male, Aging, Adolescent, Ultrasonography, Doppler, Transcranial, Siderophores, Hemodynamics, Deferoxamine, Pharmacology, Neuroprotection, Cerebral autoregulation, Article, Young Adult, chemistry.chemical_compound, medicine, Humans, Autoregulation, Erythropoietin, Aged, Aged, 80 and over, Advanced and Specialized Nursing, Cross-Over Studies, Vascular Endothelial Growth Factors, business.industry, Middle Aged, Hypoxia (medical), Chelation Therapy, Vascular endothelial growth factor, Treatment Outcome, chemistry, Cerebrovascular Circulation, Immunology, Female, Hypoxia-Inducible Factor 1, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Signal Transduction, medicine.drug |
| الوصف: | 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 P P 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.govTest . Unique identifier: NCT013655104. |
| تدمد: | 1524-4628 0039-2499 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f80050b17b8135b8f3518484bb1dba6aTest https://doi.org/10.1161/strokeaha.115.009906Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f80050b17b8135b8f3518484bb1dba6a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244628 00392499 |
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