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.
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.
Authors: Xinguo Jiang; Andrey V Malkovskiy; Wen Tian; Yon K Sung; Wenchao Sun; Joe L Hsu; Sathish Manickam; Dhananjay Wagh; Lydia-Marie Joubert; Gregg L Semenza; Jayakumar Rajadas; Mark R Nicolls Journal: Biomaterials Date: 2013-10-22 Impact factor: 12.479
Authors: Edinilton Muniz Carvalho; Lisa A Ridnour; Florêncio Sousa Gouveia Júnior; Pedro Henrique Bezerra Cabral; Nilberto Robson Falcão do Nascimento; David A Wink; Douglas W Franco; Mayara Jane Campos de Medeiros; Daniel de Lima Pontes; Elisane Longhinotti; Tércio de Freitas Paulo; Vania Bernardes-Génisson; Remi Chauvin; Eduardo Henrique Silva Sousa; Luiz Gonzaga de França Lopes Journal: J Inorg Biochem Date: 2020-06-20 Impact factor: 4.155
Authors: James R Bardill; Melissa R Laughter; Michael Stager; Kenneth W Liechty; Melissa D Krebs; Carlos Zgheib Journal: Acta Biomater Date: 2021-10-30 Impact factor: 8.947