http://www.ncbi.nlm.nih.gov/pubmed/21315355
Atherosclerosis. 2011 Jan 21. [Epub ahead of print]
Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function.
Ikeda Y, Tajima S, Yoshida S, Yamano N, Kihira Y, Ishizawa K, Aihara KI, Tomita S, Tsuchiya K, Tamaki T.
Department of Pharmacology, University of Tokushima Graduate School of Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
BACKGROUND: Deferoxamine (DFO), an iron chelator for disorders of excess iron, upregulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2), indicating that it affects angiogenesis. Herein, we clarify the effect and mechanism of action of DFO on angiogenesis.
METHODS AND RESULTS: In an in vitro study, DFO increased endothelial nitric oxide synthesis (eNOS) phosphorylation in human aortic endothelial cells (HAECs), which were inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. Tube formation, cell proliferation, and cell migration in HAECs were promoted by DFO, which were significantly reduced by LY294002. In an in vivo study, DFO promoted blood flow recovery in response to the hindlimb ischemia in mice with unilateral hindlimb surgery. The density of capillaries and arterioles in ischemic muscle was higher in DFO-treated mice compared to vehicle-treated mice. Endothelial cell proliferation increased and oxidative stress and apoptosis decreased in ischemic muscles of DFO-treated mice. The phosphorylation of Akt and eNOS on the ischemic side was elevated and urinary nitric oxide/nitric dioxide (NOx) excretion was higher in DFO-treated mice compared to vehicle-treated mice. The effect of DFO on angiogenesis was abolished in eNOS-deficient mice with hindlimb ischemia.
CONCLUSION: These findings indicate that DFO promotes revascularization via the activation of vascular endothelial cell function by an Akt-eNOS-dependent mechanism.
Deferoxamine & Angiogenesis
Deferoxamine & Angiogenesis
It's a paradigm shift
http://www.ncbi.nlm.nih.gov/pubmed/21245873
J Cereb Blood Flow Metab. 2011 Jan 19. [Epub ahead of print]
Prophylactic neuroprotection against stroke: low-dose, prolonged treatment with deferoxamine or deferasirox establishes prolonged neuroprotection independent of HIF-1 function.
Zhao Y, Rempe DA.
Department of Neurology, Center for Neural Development and Disease, The Interdepartmental Graduate Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Prophylactic neuroprotection against stroke could reduce stroke burden in thousands of patients at high risk of stroke, including those with recent transient ischemic attacks (TIAs). Prolyl hydroxylase inhibitors (PHIs), such as deferoxamine (DFO), reduce stroke volume when administered at high doses in the peristroke period, which is largely mediated by the hypoxia-inducible transcription factor (HIF-1). Yet, in vitro experiments suggest that PHIs may also induce neuroprotection independent of HIF-1. In this study, we examine chronic, prophylactic, low-dose treatment with DFO, or another iron chelator deferasirox (DFR), to determine whether they are neuroprotective with this paradigm and mediate their effects through a HIF-1-dependent mechanism. In fact, prophylactic administration of low-dose DFO or DFR significantly reduces stroke volume. Surprisingly, DFO remained neuroprotective in mice haploinsufficient for HIF-1 (HIF-1+/-) and transgenic mice with conditional loss of HIF-1 function in neurons and astrocytes. Similarly, DFR was neuroprotective in HIF-1+/- mice. Neither DFO nor DFR induced expression of HIF-1 targets. Thus, low-dose chronic administration of DFO or DFR induced a prolonged neuroprotective state independent of HIF-1 function. As DFR is an orally administered and well-tolerated medication in clinical use, it has promise for prophylaxis against stroke in patients at high risk of stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 19 January 2011; doi:10.1038/jcbfm.2010.230.
J Cereb Blood Flow Metab. 2011 Jan 19. [Epub ahead of print]
Prophylactic neuroprotection against stroke: low-dose, prolonged treatment with deferoxamine or deferasirox establishes prolonged neuroprotection independent of HIF-1 function.
Zhao Y, Rempe DA.
Department of Neurology, Center for Neural Development and Disease, The Interdepartmental Graduate Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Prophylactic neuroprotection against stroke could reduce stroke burden in thousands of patients at high risk of stroke, including those with recent transient ischemic attacks (TIAs). Prolyl hydroxylase inhibitors (PHIs), such as deferoxamine (DFO), reduce stroke volume when administered at high doses in the peristroke period, which is largely mediated by the hypoxia-inducible transcription factor (HIF-1). Yet, in vitro experiments suggest that PHIs may also induce neuroprotection independent of HIF-1. In this study, we examine chronic, prophylactic, low-dose treatment with DFO, or another iron chelator deferasirox (DFR), to determine whether they are neuroprotective with this paradigm and mediate their effects through a HIF-1-dependent mechanism. In fact, prophylactic administration of low-dose DFO or DFR significantly reduces stroke volume. Surprisingly, DFO remained neuroprotective in mice haploinsufficient for HIF-1 (HIF-1+/-) and transgenic mice with conditional loss of HIF-1 function in neurons and astrocytes. Similarly, DFR was neuroprotective in HIF-1+/- mice. Neither DFO nor DFR induced expression of HIF-1 targets. Thus, low-dose chronic administration of DFO or DFR induced a prolonged neuroprotective state independent of HIF-1 function. As DFR is an orally administered and well-tolerated medication in clinical use, it has promise for prophylaxis against stroke in patients at high risk of stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 19 January 2011; doi:10.1038/jcbfm.2010.230.
It's a paradigm shift
http://www.ncbi.nlm.nih.gov/pubmed/21278483
Exp Mol Med. 2011 Jan 31. [Epub ahead of print]
Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats.
Won SM, Lee JH, Park UJ, Gwag J, Gwag BJ, Lee YB.
Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction (TJ) proteins, occludin, and zonula occludens (ZO)-1, and degeneration of endothelial cells in the CA1-2 areas.
Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of TJ proteins and degeneration of endothelial cells, opening of the BBB after TFI.
Exp Mol Med. 2011 Jan 31. [Epub ahead of print]
Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats.
Won SM, Lee JH, Park UJ, Gwag J, Gwag BJ, Lee YB.
Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction (TJ) proteins, occludin, and zonula occludens (ZO)-1, and degeneration of endothelial cells in the CA1-2 areas.
Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of TJ proteins and degeneration of endothelial cells, opening of the BBB after TFI.
It's a paradigm shift
pair0dime, great work....
Deferoxamine has side effects and it's an injectable, if I'm remembering correctly, so it might not be one we have access to as patients. In the other thread, Cheer posted about ECGC as an alternative. I've been on ECGC but only knew it was an iron chelator; it's really exciting to learn it has these benefits for hypoxia as well.
Deferoxamine has side effects and it's an injectable, if I'm remembering correctly, so it might not be one we have access to as patients. In the other thread, Cheer posted about ECGC as an alternative. I've been on ECGC but only knew it was an iron chelator; it's really exciting to learn it has these benefits for hypoxia as well.
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I am wary of angiogenesis, knowing that it is all that stands between pre-cancer and cancer cells. Why, when LDN promotes angiogenesis, it is successful in treating cancer, remains unknown. Angiogenesis is necessary for collateral veins to grow, but they are often a poor substitute for good drainage. There also seems to be a low cancer rate in 'MS". Is angiogenesis somehow involved, i.e., when your resources are required for remedial vein growth you less typically grow tumours? Sounds like the same DNA is involved with 'MS' as with cancer. As my chemo doctor said to me about leukemia (which my brother had) and MS, they may be two sides of the same coin.
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Not a doctor.
"I'm still here, how 'bout that? I may have lost my lunchbox, but I'm still here." John Cowan Hartford (December 30, 1937 – June 4, 2001)
Not a doctor.
"I'm still here, how 'bout that? I may have lost my lunchbox, but I'm still here." John Cowan Hartford (December 30, 1937 – June 4, 2001)
I am much more comfortable with the idea of taking 600mg EGCG (green tea extract) per day as I do....along with other vitamins & supplements that promote good endothelial health. Of course, correcting any venous malformations that impede cerebrospinal venous drainage and optimizing flow is essential.
It's a paradigm shift