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Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication
Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713368/ https://www.ncbi.nlm.nih.gov/pubmed/36459715 http://dx.doi.org/10.1016/j.redox.2022.102521 |
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author | Huang, Kai Wu, Yusi Zhang, Yixuan Youn, Ji Youn Cai, Hua |
author_facet | Huang, Kai Wu, Yusi Zhang, Yixuan Youn, Ji Youn Cai, Hua |
author_sort | Huang, Kai |
collection | PubMed |
description | Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H(4)B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers. |
format | Online Article Text |
id | pubmed-9713368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97133682022-12-02 Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication Huang, Kai Wu, Yusi Zhang, Yixuan Youn, Ji Youn Cai, Hua Redox Biol Research Paper Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H(4)B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers. Elsevier 2022-11-16 /pmc/articles/PMC9713368/ /pubmed/36459715 http://dx.doi.org/10.1016/j.redox.2022.102521 Text en © 2022 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Huang, Kai Wu, Yusi Zhang, Yixuan Youn, Ji Youn Cai, Hua Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
title | Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
title_full | Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
title_fullStr | Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
title_full_unstemmed | Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
title_short | Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
title_sort | combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713368/ https://www.ncbi.nlm.nih.gov/pubmed/36459715 http://dx.doi.org/10.1016/j.redox.2022.102521 |
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