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ATHEROSCLEROSIS / RESEARCH PAPER
Beneficial Effects of Antioxidants in Regulating NET Generation Within the Course of Atherosclerosis
1
Medical Analysis Laboratory ALAB laboratory Sp. z o.o., T. Kwiatkowskiego 19, 06-102 Pułtusk,, Poland
2
Department of Immunology, Medical University of Bialystok, J. Waszyngtona 15A, 15-269 Bialystok,, Poland
3
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, J. Waszyngtona 13, 15-269, Bialystok,, Poland
4
Regional Centre for Transfusion Medicine, Bialystok, M. Skłodowskiej-Curie 23, 15-950, Bialystok,, Poland
5
Department of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, M. Skłodowskiej-Curie 24a, 15-276, Bialystok,, Poland
6
Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, M. Skłodowskiej-Curie 24 A, 15-276 Bialystok,, Poland
Submission date: 2025-07-15
Final revision date: 2025-10-01
Acceptance date: 2025-10-29
Publication date: 2025-11-28
Corresponding author
Dorota Dąbrowska-Zagroba
Medical Analysis Laboratory ALAB laboratory Sp. z o.o., T. Kwiatkowskiego 19, 06-102 Pułtusk,, Poland
Medical Analysis Laboratory ALAB laboratory Sp. z o.o., T. Kwiatkowskiego 19, 06-102 Pułtusk,, Poland
KEYWORDS
TOPICS
ABSTRACT
Introduction:
There are numerous publications confirming the involvement of neutrophils in the pathomechanism of atherosclerosis. The aim of this study was to determine the effects of flavonoids (quercetin and luteolin) and vitamin C on neutrophil extracellular trap (NET) formation and regulation of NET markers, including circulating free DNA (cfDNA) and myeloperoxidase (MPO). Additionally, we assessed the expression of NADPH oxidase complex subunits and superoxide anion generation in neutrophils.
Material and methods:
Whole blood samples were collected from patients with atherosclerosis. Neutrophils were stimulated with lipopolysaccharide (LPS), and the effects of flavonoids and vitamin C on NET release, NADPH oxidase subunit expression (p47phox, p67phox, Rac1), and superoxide production were evaluated.
Results:
Atherosclerotic patients showed increased NETosis, with elevated NET release, MPO, and cfDNA levels. Expression of NADPH oxidase subunits p47phox and p67phox, as well as superoxide anion generation, were significantly higher compared to controls. LPS further enhanced these effects. Treatment with quercetin, luteolin, and vitamin C reduced NET formation, NADPH oxidase expression, and superoxide production in stimulated neutrophils.
Conclusions:
Flavonoids and vitamin C modulate NET generation by affecting NADPH oxidase activity and reactive oxygen species production, suggesting potential therapeutic use in atherosclerosis. Further and more detailed analysis could allow for the potential application of these compounds as adjunctive therapy in the treatment of atherosclerosis.
There are numerous publications confirming the involvement of neutrophils in the pathomechanism of atherosclerosis. The aim of this study was to determine the effects of flavonoids (quercetin and luteolin) and vitamin C on neutrophil extracellular trap (NET) formation and regulation of NET markers, including circulating free DNA (cfDNA) and myeloperoxidase (MPO). Additionally, we assessed the expression of NADPH oxidase complex subunits and superoxide anion generation in neutrophils.
Material and methods:
Whole blood samples were collected from patients with atherosclerosis. Neutrophils were stimulated with lipopolysaccharide (LPS), and the effects of flavonoids and vitamin C on NET release, NADPH oxidase subunit expression (p47phox, p67phox, Rac1), and superoxide production were evaluated.
Results:
Atherosclerotic patients showed increased NETosis, with elevated NET release, MPO, and cfDNA levels. Expression of NADPH oxidase subunits p47phox and p67phox, as well as superoxide anion generation, were significantly higher compared to controls. LPS further enhanced these effects. Treatment with quercetin, luteolin, and vitamin C reduced NET formation, NADPH oxidase expression, and superoxide production in stimulated neutrophils.
Conclusions:
Flavonoids and vitamin C modulate NET generation by affecting NADPH oxidase activity and reactive oxygen species production, suggesting potential therapeutic use in atherosclerosis. Further and more detailed analysis could allow for the potential application of these compounds as adjunctive therapy in the treatment of atherosclerosis.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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