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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...

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Autores principales: Huang, Kai, Wu, Yusi, Zhang, Yixuan, Youn, Ji Youn, Cai, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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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