Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1)
| العنوان: | Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1) |
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| المؤلفون: | Azza B. El-Remessy, Ahmed Y. Shanab, Susan C. Fagan, Sahar Soliman, Harika Sabbineni, Sally L. Elshaer, Suraporn Matragoon, Mona F. El-Azab |
| المصدر: | Angiogenesis. 18:137-150 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Cancer Research, medicine.medical_specialty, Physiology, Angiogenesis, Clinical Biochemistry, Ischemia, Nitric Oxide Synthase Type II, Tetrazoles, Article, Neovascularization, Mice, chemistry.chemical_compound, Retinal Diseases, Internal medicine, medicine, Animals, Gene Silencing, Neovascularization, Pathologic, biology, business.industry, Biphenyl Compounds, Kinase insert domain receptor, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Mice, Inbred C57BL, Vascular endothelial growth factor, Nitric oxide synthase, Oxidative Stress, Candesartan, Vascular endothelial growth factor A, Endocrinology, chemistry, biology.protein, Benzimidazoles, medicine.symptom, business, Angiotensin II Type 1 Receptor Blockers, Heme Oxygenase-1, medicine.drug |
| الوصف: | Ischemic diseases such as stroke and proliferative retinopathy are characterized by hypoxia-driven release of angiogenic factors such as vascular endothelial growth factor (VEGF). However, revascularization of the ischemic areas is inadequate, resulting in impaired neuro-vascular function. We aim to examine the vascular protective effects of candesartan, an angiotensin receptor blocker, in an ischemic retinopathy mouse model. Vascular density, number of tip cells, and perfusions of capillaries were assessed. Activation of Muller glial cells and levels of peroxynitrite, VEGF, VEGFR2, inducible nitric oxide synthase, hemeoxygenase-1 (HO-1) were assessed. Proangiogenic effects of candesartan were examined in human endothelial cells (EC) that were cultured in normoxia or hypoxia and transduced with siRNA against HO-1. Candesartan (1 mg/kg) and (10 mg/kg) decreased hypoxia-induced neovascularization by 67 and 70%, respectively. Candesartan (10 mg/kg) significantly stimulated the number of tip cells and physiological revascularization of the central retina (45%) compared with untreated pups. The effects of candesartan coincided with reduction of hypoxia-induced Muller glial activation, iNOS expression and restoration of HO-1 expression with no significant change in VEGF levels. In vitro, silencing HO-1 expression blunted the ability of candesartan to induce VEGF expression under normoxia and VEGFR2 activation and angiogenic response under both normoxia and hypoxia. These findings suggest that candesartan improved reparative angiogenesis and hence prevented pathological angiogenesis by modulating HO-1 and iNOS levels in ischemic retinopathy. HO-1 is required for VEGFR2 activation and proangiogenic action of candesartan in EC. Candesartan, an FDA-approved drug, could be repurposed as a potential therapeutic agent for the treatment of ischemic diseases. |
| تدمد: | 1573-7209 0969-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::529de4d13c6cb52b08d300e3da4175beTest https://doi.org/10.1007/s10456-014-9451-4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....529de4d13c6cb52b08d300e3da4175be |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15737209 09696970 |
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