Search
Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets
Abstract
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.
Citations
-
6 0
CrossRef
-
0
Web of Science
-
5 6
Scopus
Authors (5)
-
Anna Janaszak-Jasiecka
-
Agata Płoska
-
Joanna M. Wierońska
-
Lawrence W. Dobrucki
Cite as
Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.1186/s11658-023-00423-2
- License
-
open in new tab
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
CELLULAR & MOLECULAR BIOLOGY LETTERS
no. 28,
ISSN: 1425-8153 - Language:
- English
- Publication year:
- 2023
- Bibliographic description:
- 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:
- Digital Object Identifier (open in new tab) 10.1186/s11658-023-00423-2
- Sources of funding:
-
- 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.
- Verified by:
- Gdańsk University of Technology
seen 59 times
Recommended for you
Endothelial Dysfunction Driven by Hypoxia—The Influence of Oxygen Deficiency on NO Bioavailability
- A. Janaszak-Jasiecka,
- A. Siekierzycka,
- A. Płoska
- + 2 authors
Anti-cancer effect of Rumex obtusifolius in combination with arginase/nitric oxide synthase inhibitors via downregulation of oxidative stress, inflammation, and polyamine synthesis
- M. Ginovyan,
- H. Javrushyan,
- G. Petrosyan
- + 10 authors
Procognitive activity of nitric oxide inhibitors and donors in animal models
- P. Cieślik,
- L. Kalinowski,
- J. M. Wierońska
Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia
- J. M. Wierońska,
- P. Cieślik,
- L. Kalinowski