Molecular mechanisms underlying the activation of eNOS
Abstract
Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro- and anti-atherosclerotic genes. Many of these effects are mediated by changes in the generation and release of the vasodilator nitric oxide (NO) in response to hemodynamic stimuli exerted on the luminal surface of endothelial cells by the streaming blood (shear stress) and the cyclic strain of the vascular wall. The endothelial NO synthase (eNOS) is activated in response to fluid shear stress and numerous agonists via cellular events such as; increased intracellular Ca(2+), interaction with substrate and co-factors, as well as adaptor and regulatory proteins, protein phosphorylation, and through shuttling between distinct sub-cellular domains. Dysregulation of these processes leads to attenuated eNOS activity and reduced NO output which is a characteristic feature of numerous patho-physiological disorders such as diabetes and atherosclerosis. This review summarizes some of the recent findings relating to the molecular events regulating eNOS activity.
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eNOS is constitutively expressed, and posttranslational modifications impact its ability to produce NO, from changes in NO production rates to complete blockade of NO synthesis.
“eNOS is constitutively expressed; a number of posttranslational modifications impact the ability of eNOS to produce NO, from changes in the NO production rates to, in some cases, the complete blockade of NO synthesis”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [296]
PYK2 is activated in endothelial cells by angiotensin II, oxidative stress, and insulin.
“This kinase is activated in endothelial cells by several stimuli including angiotensin II, oxidative stress, and insulin”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [296]
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- Authors
- Fleming, I.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Fleming, Ingrid
- ORCID
- Fleming, Ingrid
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2009-12-13
- Volume
- 459
- Issue
- 6
- Pages
- 793-806
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2000165700
- Cited by
- 437
- References
- 125
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 22 · 2023: 20 · 2022: 20 · 2021: 27 · 2020: 33 · 2019: 32 · 2018: 29 · 2017: 31 · 2016: 32 · 2015: 32 · 2014: 35 · 2013: 23 · 2012: 44
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- endothelial nitric oxide synthase, eNOS activation, nitric oxide, endothelial cells, fluid shear stress, cyclic strain, intracellular calcium, protein phosphorylation, adaptor proteins, atherosclerosis, diabetes mellitus, vascular tone, hemodynamics
- MeSH terms
- Soluble Guanylyl Cyclase, Amino Acid Sequence, Biopterins, Calmodulin, Enzyme Activation, Guanylate Cyclase, Humans, Nitric Oxide, Phosphorylation, Protein Kinases, Signal Transduction, Receptors, Cytoplasmic and Nuclear, HSP90 Heat-Shock Proteins, Platelet Endothelial Cell Adhesion Molecule-1, Dynamins, Adaptor Proteins, Signal Transducing, Caveolin 1, Nitric Oxide Synthase Type III, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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