Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases

Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases

Alamzeb Khan, Hazem Dawoud, Tadeusz Malinski Department of Chemistry & Biochemistry, Nanomedical Research Laboratories, Ohio University, Athens, OH, USA Background: Clinical studies indicate that vitamin D3 improves circulation and may have beneficial effects in hypertension. This study us...

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Autores principales: Khan A, Dawoud H, Malinski T
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
Vitamin D3
hypertension
nitric oxide
peroxynitrite
angiotensin II
endothelial dysfunction
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/77f0a767a435405bbe39bbc50ee249a6
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spelling oai:doaj.org-article:77f0a767a435405bbe39bbc50ee249a62021-12-02T01:32:22ZNanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases1178-2013https://doaj.org/article/77f0a767a435405bbe39bbc50ee249a62018-01-01T00:00:00Zhttps://www.dovepress.com/nanomedical-studies-of-the-restoration-of-nitric-oxideperoxynitrite-ba-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alamzeb Khan, Hazem Dawoud, Tadeusz Malinski Department of Chemistry & Biochemistry, Nanomedical Research Laboratories, Ohio University, Athens, OH, USA Background: Clinical studies indicate that vitamin D3 improves circulation and may have beneficial effects in hypertension. This study uses nanomedical systems to investigate the role of 1,25-dihydroxy vitamin D3 in the preservation/restoration of endothelial function in an angiotensin II (Ang II) cellular model of hypertension. Methods: 1,25-dihydroxy vitamin D3-stimulated nitric oxide (NO) and peroxynitrite (ONOO-) concentrations were measured in situ with nanosensors (200–300 mm diameter with a detection limit of 1 nM) in human umbilical vein endothelial cells of African American (AA) and Caucasian American (CA) donors exposed to Ang II. The balance/imbalance between NO and ONOO- concentrations ([NO]/[ONOO-]) was simultaneously monitored and used as an indicator of endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction. Results: [NO]/[ONOO-] imbalance in Ang II-stimulated dysfunctional endothelium was 0.20±0.16 for CAs and 0.11±0.09 for AAs. Uncoupled eNOS and overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contributed to high production of ONOO-. Vitamin D3 treatment reversed [NO]/[ONOO-] to 3.0±0.1 in CAs and 2.1±0.1 in AAs – exceeding that observed in normal endothelium. Vitamin D3 restored uncoupled eNOS and endothelial function by increasing cytoprotective NO and decreasing the cytotoxic ONOO-. The beneficial effect of vitamin D3 is associated with a favorable rate of NO and ONOO- release, restoration of the [NO]/[ONOO-] and the overall decrease in the overexpression of eNOS, inducible nitric oxide synthase and NADPH oxidase. This effect of vitamin D3 may prove to be beneficial in the treatment of hypertension and other cardiovascular diseases, including heart failure, myocardial infarction, vasculopathy, stroke and diabetes. Keywords: vitamin D3, hypertension, nitric oxide, peroxynitrite, endothelial dysfunction, nanomedicine, restoration of endotheliumKhan ADawoud HMalinski TDove Medical PressarticleVitamin D3hypertensionnitric oxideperoxynitriteangiotensin IIendothelial dysfunctionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 455-466 (2018)
institution DOAJ
collection DOAJ
language EN
topic Vitamin D3
hypertension
nitric oxide
peroxynitrite
angiotensin II
endothelial dysfunction
Medicine (General)
R5-920
spellingShingle Vitamin D3
hypertension
nitric oxide
peroxynitrite
angiotensin II
endothelial dysfunction
Medicine (General)
R5-920
Khan A
Dawoud H
Malinski T
Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases
description Alamzeb Khan, Hazem Dawoud, Tadeusz Malinski Department of Chemistry & Biochemistry, Nanomedical Research Laboratories, Ohio University, Athens, OH, USA Background: Clinical studies indicate that vitamin D3 improves circulation and may have beneficial effects in hypertension. This study uses nanomedical systems to investigate the role of 1,25-dihydroxy vitamin D3 in the preservation/restoration of endothelial function in an angiotensin II (Ang II) cellular model of hypertension. Methods: 1,25-dihydroxy vitamin D3-stimulated nitric oxide (NO) and peroxynitrite (ONOO-) concentrations were measured in situ with nanosensors (200–300 mm diameter with a detection limit of 1 nM) in human umbilical vein endothelial cells of African American (AA) and Caucasian American (CA) donors exposed to Ang II. The balance/imbalance between NO and ONOO- concentrations ([NO]/[ONOO-]) was simultaneously monitored and used as an indicator of endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction. Results: [NO]/[ONOO-] imbalance in Ang II-stimulated dysfunctional endothelium was 0.20±0.16 for CAs and 0.11±0.09 for AAs. Uncoupled eNOS and overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contributed to high production of ONOO-. Vitamin D3 treatment reversed [NO]/[ONOO-] to 3.0±0.1 in CAs and 2.1±0.1 in AAs – exceeding that observed in normal endothelium. Vitamin D3 restored uncoupled eNOS and endothelial function by increasing cytoprotective NO and decreasing the cytotoxic ONOO-. The beneficial effect of vitamin D3 is associated with a favorable rate of NO and ONOO- release, restoration of the [NO]/[ONOO-] and the overall decrease in the overexpression of eNOS, inducible nitric oxide synthase and NADPH oxidase. This effect of vitamin D3 may prove to be beneficial in the treatment of hypertension and other cardiovascular diseases, including heart failure, myocardial infarction, vasculopathy, stroke and diabetes. Keywords: vitamin D3, hypertension, nitric oxide, peroxynitrite, endothelial dysfunction, nanomedicine, restoration of endothelium
format article
author Khan A
Dawoud H
Malinski T
author_facet Khan A
Dawoud H
Malinski T
author_sort Khan A
title Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases
title_short Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases
title_full Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases
title_fullStr Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases
title_full_unstemmed Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases
title_sort nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin d3 – clinical implications for cardiovascular diseases
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/77f0a767a435405bbe39bbc50ee249a6
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AT dawoudh nanomedicalstudiesoftherestorationofnitricoxideperoxynitritebalanceindysfunctionalendotheliumby125dihydroxyvitamind3ndashclinicalimplicationsforcardiovasculardiseases
AT malinskit nanomedicalstudiesoftherestorationofnitricoxideperoxynitritebalanceindysfunctionalendotheliumby125dihydroxyvitamind3ndashclinicalimplicationsforcardiovasculardiseases
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