Cited by 437Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionAngiogenesis and VEGF in Cancer

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Molecular mechanisms underlying the activation of eNOS

Fleming, Ingrid·2010·Pflügers Archiv - European Journal of Physiology

DOI 10.1007/s00424-009-0767-7

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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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Authors: Fleming, I.
Affiliations: Goethe University Frankfurt (DE)
Corresponding author: Fleming, Ingrid
ORCID: Fleming, Ingrid
Venue: Pflügers Archiv - European Journal of Physiology
Publisher: Springer Science and Business Media LLC
Published: 2009-12-13
Volume: 459
Issue: 6
Pages: 793-806
ISSN: 0031-6768 (ISSN-L)
1432-2013
DOI: 10.1007/s00424-009-0767-7
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 (medical) › 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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