Cargando…
Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD
BACKGROUNDS: Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610829/ https://www.ncbi.nlm.nih.gov/pubmed/29081889 http://dx.doi.org/10.1155/2017/6210694 |
_version_ | 1783265833283223552 |
---|---|
author | Mao, Ke Shu, Wanting Liu, Libin Gu, Qing Qiu, Qinghua Wu, XingWei |
author_facet | Mao, Ke Shu, Wanting Liu, Libin Gu, Qing Qiu, Qinghua Wu, XingWei |
author_sort | Mao, Ke |
collection | PubMed |
description | BACKGROUNDS: Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. METHODS: C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. CYLD siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression. RESULTS: OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction. CONCLUSIONS: We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD. |
format | Online Article Text |
id | pubmed-5610829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-56108292017-10-29 Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD Mao, Ke Shu, Wanting Liu, Libin Gu, Qing Qiu, Qinghua Wu, XingWei Oxid Med Cell Longev Research Article BACKGROUNDS: Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. METHODS: C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. CYLD siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression. RESULTS: OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction. CONCLUSIONS: We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD. Hindawi 2017 2017-09-01 /pmc/articles/PMC5610829/ /pubmed/29081889 http://dx.doi.org/10.1155/2017/6210694 Text en Copyright © 2017 Ke Mao et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Mao, Ke Shu, Wanting Liu, Libin Gu, Qing Qiu, Qinghua Wu, XingWei Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD |
title | Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD |
title_full | Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD |
title_fullStr | Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD |
title_full_unstemmed | Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD |
title_short | Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD |
title_sort | salvianolic acid a inhibits ox-ldl effects on exacerbating choroidal neovascularization via downregulating cyld |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610829/ https://www.ncbi.nlm.nih.gov/pubmed/29081889 http://dx.doi.org/10.1155/2017/6210694 |
work_keys_str_mv | AT maoke salvianolicacidainhibitsoxldleffectsonexacerbatingchoroidalneovascularizationviadownregulatingcyld AT shuwanting salvianolicacidainhibitsoxldleffectsonexacerbatingchoroidalneovascularizationviadownregulatingcyld AT liulibin salvianolicacidainhibitsoxldleffectsonexacerbatingchoroidalneovascularizationviadownregulatingcyld AT guqing salvianolicacidainhibitsoxldleffectsonexacerbatingchoroidalneovascularizationviadownregulatingcyld AT qiuqinghua salvianolicacidainhibitsoxldleffectsonexacerbatingchoroidalneovascularizationviadownregulatingcyld AT wuxingwei salvianolicacidainhibitsoxldleffectsonexacerbatingchoroidalneovascularizationviadownregulatingcyld |