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Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets
Abstrakt
Nitric oxide (NO) is one of the most important molecules released by endothelial cells, and its antiatherogenic properties support cardiovascular homeostasis. Diminished NO bioavailability is a common hallmark of endothelial dysfunction underlying the patho‑ genesis of the cardiovascular disease. Vascular NO is synthesized by endothelial nitric oxide synthase (eNOS) from the substrate L‑arginine (L‑Arg), with tetrahydrobiopterin (BH4) as an essential cofactor. Cardiovascular risk factors such as diabetes, dyslipidemia, hypertension, aging, or smoking increase vascular oxidative stress that strongly affects eNOS activity and leads to eNOS uncoupling. Uncoupled eNOS produces superoxide anion (O2−) instead of NO, thus becoming a source of harmful free radicals exacerbat‑ ing the oxidative stress further. eNOS uncoupling is thought to be one of the major underlying causes of endothelial dysfunction observed in the pathogenesis of vascular diseases. Here, we discuss the main mechanisms of eNOS uncoupling, including oxida‑ tive depletion of the critical eNOS cofactor BH4, deficiency of eNOS substrate L‑Arg, or accumulation of its analog asymmetrical dimethylarginine (ADMA), and eNOS S‑glu‑ tathionylation. Moreover, potential therapeutic approaches that prevent eNOS uncou‑ pling by improving cofactor availability, restoration of L‑Arg/ADMA ratio, or modulation of eNOS S‑glutathionylation are briefly outlined.
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Autorzy (5)
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Anna Janaszak-Jasiecka
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Agata Płoska
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Joanna M. Wierońska
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Lawrence W. Dobrucki
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Pełna treść
- Wersja publikacji
- Accepted albo Published Version
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1186/s11658-023-00423-2
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Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
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CELLULAR & MOLECULAR BIOLOGY LETTERS
nr 28,
ISSN: 1425-8153 - Język:
- angielski
- Rok wydania:
- 2023
- Opis bibliograficzny:
- Janaszak-Jasiecka A., Płoska A., Wierońska J. M., Dobrucki L. W., Kalinowski L.: Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets// CELLULAR & MOLECULAR BIOLOGY LETTERS -Vol. 28,iss. 1 (2023),
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1186/s11658-023-00423-2
- Źródła finansowania:
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- This study was supported by the Polish National Science Centre (NCN) OPUS Grant Nos. 2015/19/B/NZ7/03830 and 2019/33/B/NZ7/02699, and by the Ministry of Education and Science Poland Grant No. 10/E‑389/SPUB/SP/2020.
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 61 razy
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