Biological Assessment of the NO-Dependent Endothelial Function

Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venou...

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Main Authors: Hasnae Boughaleb, Irina Lobysheva, Flavia Dei Zotti, Jean-Luc Balligand, Virginie Montiel
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/22/7921
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author Hasnae Boughaleb
Irina Lobysheva
Flavia Dei Zotti
Jean-Luc Balligand
Virginie Montiel
author_facet Hasnae Boughaleb
Irina Lobysheva
Flavia Dei Zotti
Jean-Luc Balligand
Virginie Montiel
author_sort Hasnae Boughaleb
collection DOAJ
description Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.
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spelling doaj.art-a82bde15917c4e48875801e044c15e1d2023-11-24T09:23:25ZengMDPI AGMolecules1420-30492022-11-012722792110.3390/molecules27227921Biological Assessment of the NO-Dependent Endothelial FunctionHasnae Boughaleb0Irina Lobysheva1Flavia Dei Zotti2Jean-Luc Balligand3Virginie Montiel4Pole of Pharmacology and Therapeutics (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumPole of Pharmacology and Therapeutics (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumPole of Pharmacology and Therapeutics (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumPole of Pharmacology and Therapeutics (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumPole of Pharmacology and Therapeutics (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumNitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.https://www.mdpi.com/1420-3049/27/22/7921nitric oxideNO-dependent endothelial functionNO bioavailabilityendothelial dysfunctionnitrosylated hemoglobinHbNO
spellingShingle Hasnae Boughaleb
Irina Lobysheva
Flavia Dei Zotti
Jean-Luc Balligand
Virginie Montiel
Biological Assessment of the NO-Dependent Endothelial Function
Molecules
nitric oxide
NO-dependent endothelial function
NO bioavailability
endothelial dysfunction
nitrosylated hemoglobin
HbNO
title Biological Assessment of the NO-Dependent Endothelial Function
title_full Biological Assessment of the NO-Dependent Endothelial Function
title_fullStr Biological Assessment of the NO-Dependent Endothelial Function
title_full_unstemmed Biological Assessment of the NO-Dependent Endothelial Function
title_short Biological Assessment of the NO-Dependent Endothelial Function
title_sort biological assessment of the no dependent endothelial function
topic nitric oxide
NO-dependent endothelial function
NO bioavailability
endothelial dysfunction
nitrosylated hemoglobin
HbNO
url https://www.mdpi.com/1420-3049/27/22/7921
work_keys_str_mv AT hasnaeboughaleb biologicalassessmentofthenodependentendothelialfunction
AT irinalobysheva biologicalassessmentofthenodependentendothelialfunction
AT flaviadeizotti biologicalassessmentofthenodependentendothelialfunction
AT jeanlucballigand biologicalassessmentofthenodependentendothelialfunction
AT virginiemontiel biologicalassessmentofthenodependentendothelialfunction