Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease

Duffy, Stephen J.; Biegelsen, Elizabeth S.; Holbrook, Monika; Russell, J.D.; Gokce, Noyan; Keaney, John F.; Vita, Joseph A.

doi:10.1161/01.cir.103.23.2799

Cited by 238 publications

(152 citation statements)

References 42 publications

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“…In the clinical setting, sequestering free iron released during cold storage is possible, and such a strategy may prove to be useful as suggested by our work in the rat transplant model (25). Although iron chelators including deferoxamine have been used in a number of clinical studies (13,40,58,73), no published studies to our knowledge have addressed the efficacy of similar agents in cold ischemic injury of human organs removed for transplantation. While deferoxamine's protective effect that we found in the transplant model against cold is considered mainly due to its antioxidant properties (25), other effects of deferoxamine such as upregulation of cytoprotective genes, HO-1, EPO, and VGEF via HIF-I transcription factor are to be (3,76).…”

Section: Free Iron Release During Cold Storage: a Clinically Addressamentioning

confidence: 98%

Cold ischemic injury of transplanted kidneys: new insights from experimental studies

Salahudeen¹

2004

American Journal of Physiology-Renal Physiology

144

128

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Kidney transplantation is the preferred and definitive treatment for end-stage renal disease (ESRD), and kidneys from deceased donors are a major source for it. These kidneys are routinely cold stored to prolong viability, which, however, when prolonged can cause injury, resulting in reduced graft function and survival. Recent experimental studies have identified the release of iron and free radicals, activation of calpain, and formation of F2-isoprostanes as important components of cold ischemic injury, as are the swelling of mitochondria and activation of mitochondrial apoptotic pathways. Moreover, studies have also suggested that fortifying the storage solution with deferoxamine or preconditioning the donor kidneys with hemeoxygenase-1 may prove viable clinical strategies to limit cold ischemic injury. This review will summarize these and other new experimental data that have implications for reducing cold ischemic transplant injury, a step necessary to improve deceased-donor allograft survival.

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Section: Free Iron Release During Cold Storage: a Clinically Addressamentioning

confidence: 98%

Cold ischemic injury of transplanted kidneys: new insights from experimental studies

Salahudeen¹

2004

American Journal of Physiology-Renal Physiology

144

128

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“…Accordingly, benefit may be derived from iron chelation. Fifteen years ago, it was shown that iron chelation improves endothelial function in patients with coronary artery disease [10]. Deferoxamine improved nitric-oxidemediated, endothelium-dependent vasodilation, suggesting that iron availability contributes to impaired nitric-oxide action in atherosclerosis.…”

Section: Clinical Consequences Of Iron Overload In Mdsmentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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“…161 Finally, when patients with coronary artery disease and control patients were infused with DES (500 mg during 1 h), a significant drop in serum iron concentrations was observed. 162 In addition, a significant increase in resting forearm blood flow was noted immediately after the start of infusion in both groups, and it persisted for the entire period of infusion.…”

Section: Iron-related Neurotherapeuticsmentioning

confidence: 83%

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

et al. 2007

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Summary:Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathological processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article, we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development.

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Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease

Abstract: Deferoxamine improved nitric oxide-mediated, endothelium-dependent vasodilation in patients with coronary artery disease. These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.

Cited by 238 publications

References 42 publications

Cold ischemic injury of transplanted kidneys: new insights from experimental studies

Cold ischemic injury of transplanted kidneys: new insights from experimental studies

Iron overload in myelodysplastic syndromes (MDS)

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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