Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy.
<h4>Background</h4>Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin del...
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2010
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oai:doaj.org-article:1885caee1bc448fabe094558a6c735e62021-11-18T06:36:34ZDifferential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy.1932-620310.1371/journal.pone.0011870https://doaj.org/article/1885caee1bc448fabe094558a6c735e62010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20686695/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models.<h4>Methodology/principal findings</h4>The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001).<h4>Conclusions</h4>This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs.Carmel M McVicarLiza M ColhounJodie L AbrahamsClaire L KitsonRoss HamiltonReinhold J MedinaDash DurgaTom A GardinerPauline M RuddAlan W StittPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11870 (2010) |
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Medicine R Science Q Carmel M McVicar Liza M Colhoun Jodie L Abrahams Claire L Kitson Ross Hamilton Reinhold J Medina Dash Durga Tom A Gardiner Pauline M Rudd Alan W Stitt Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| description |
<h4>Background</h4>Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models.<h4>Methodology/principal findings</h4>The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001).<h4>Conclusions</h4>This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs. |
| format |
article |
| author |
Carmel M McVicar Liza M Colhoun Jodie L Abrahams Claire L Kitson Ross Hamilton Reinhold J Medina Dash Durga Tom A Gardiner Pauline M Rudd Alan W Stitt |
| author_facet |
Carmel M McVicar Liza M Colhoun Jodie L Abrahams Claire L Kitson Ross Hamilton Reinhold J Medina Dash Durga Tom A Gardiner Pauline M Rudd Alan W Stitt |
| author_sort |
Carmel M McVicar |
| title |
Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| title_short |
Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| title_full |
Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| title_fullStr |
Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| title_full_unstemmed |
Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| title_sort |
differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/1885caee1bc448fabe094558a6c735e6 |
| work_keys_str_mv |
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