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Low-grade endotoxemia and NOX-2 in patients with coronary microvascular angina

Lorenzo Loffredo1, Victoria Ivanov2, Nicolae Ciobanu2, Micaela Ivanov2, Paolo Ciacci1, Cristina Nocella1, Vittoria Cammisotto1, Federica Orlando1, Aurora Paraninfi1, Enrico Maggio1, Alessandra D’Amico3, Paolo Rosa4, Mihail Popovici2, Simona Bartimoccia1, Francesco Barillà5, Elena Deseatnicova6, Evgenii Gutu7, Francesco Violi89, Roberto Carnevale49
DOI: 10.33963/KP.a2022.0130
·
Pubmed: 35579023
Affiliations
  1. Department of Clinical, Internistic, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
  2. Moldavian Research Institute of Cardiology, Chisinau, Republic of Moldova
  3. Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
  4. Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
  5. Dipartimento di Medicina dei Sistemi, Università degli Studi “Tor Vergata”, Roma, Italy
  6. Department of Rheumatology and Nephrology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, Chisinau, Republic of Moldova
  7. 3rd Department of General Surgery, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, Chisinau, Republic of Moldova
  8. Sapienza University, Rome, Italy
  9. Mediterranea Cardiocentro, Napoli, Italy

open access

Online first
Original article
Published online: 2022-05-17

Abstract

BACKGROUND: Endothelial dysfunction and oxidative stress were hypothesized to be involved in the pathogenesis of coronary microvascular angina (MVA). NADPH oxidase-2 (NOX2) activation could provoke increased oxidative stress and endothelial dysfunction but data in MVA have not been provided yet.

AIMS: The aim of this study was to evaluate the interaction among NOX2 activation, serum lipopolysaccharide (LPS) levels as well as oxidative stress production as potential causes of endothelial dysfunction in MVA patients.

METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), nitric oxide (NO) bioavailability, endothelin-1 (ET-1), serum zonulin (as intestinal permeability assay)  and LPS in 80 consecutive subjects, including 40 MVA patients and 40 controls (CT)  matched for age and gender.

RESULTS: Compared with CT, MVA patients had significant higher values of sNOX-2-dp, H2O2, ET-1, LPS and zonulin; conversely HBA and NO bioavailability was significantly lower in MVA patients. Simple linear regression analysis showed that sNOX2 was associated with serum LPS, serum zonulin, H2O2 and ET-1; furthermore, an inverse correlation between sNOX2 and HBA and nitric oxide bioavailability was observed. Multiple linear regression analysis showed that LPS and zonulin emerged as the only independent predictive variables associated with sNOX2.

CONCLUSIONS: this study provides the first report attesting that patients with MVA have high LPS levels, NOX-2 activation and an imbalance between pro-oxidant and antioxidant systems, in favor of the oxidizing molecules that could be potentially implicated in the endothelial dysfunction and vasoconstriction of this disease.

Abstract

BACKGROUND: Endothelial dysfunction and oxidative stress were hypothesized to be involved in the pathogenesis of coronary microvascular angina (MVA). NADPH oxidase-2 (NOX2) activation could provoke increased oxidative stress and endothelial dysfunction but data in MVA have not been provided yet.

AIMS: The aim of this study was to evaluate the interaction among NOX2 activation, serum lipopolysaccharide (LPS) levels as well as oxidative stress production as potential causes of endothelial dysfunction in MVA patients.

METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), nitric oxide (NO) bioavailability, endothelin-1 (ET-1), serum zonulin (as intestinal permeability assay)  and LPS in 80 consecutive subjects, including 40 MVA patients and 40 controls (CT)  matched for age and gender.

RESULTS: Compared with CT, MVA patients had significant higher values of sNOX-2-dp, H2O2, ET-1, LPS and zonulin; conversely HBA and NO bioavailability was significantly lower in MVA patients. Simple linear regression analysis showed that sNOX2 was associated with serum LPS, serum zonulin, H2O2 and ET-1; furthermore, an inverse correlation between sNOX2 and HBA and nitric oxide bioavailability was observed. Multiple linear regression analysis showed that LPS and zonulin emerged as the only independent predictive variables associated with sNOX2.

CONCLUSIONS: this study provides the first report attesting that patients with MVA have high LPS levels, NOX-2 activation and an imbalance between pro-oxidant and antioxidant systems, in favor of the oxidizing molecules that could be potentially implicated in the endothelial dysfunction and vasoconstriction of this disease.

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Keywords

coronary microvascular angina, LPS, NADPH oxidase, NOX2, oxidative stress

About this article
Title

Low-grade endotoxemia and NOX-2 in patients with coronary microvascular angina

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Online first

Article type

Original article

Published online

2022-05-17

Page views

107

Article views/downloads

88

DOI

10.33963/KP.a2022.0130

Pubmed

35579023

Keywords

coronary microvascular angina
LPS
NADPH oxidase
NOX2
oxidative stress

Authors

Lorenzo Loffredo
Victoria Ivanov
Nicolae Ciobanu
Micaela Ivanov
Paolo Ciacci
Cristina Nocella
Vittoria Cammisotto
Federica Orlando
Aurora Paraninfi
Enrico Maggio
Alessandra D’Amico
Paolo Rosa
Mihail Popovici
Simona Bartimoccia
Francesco Barillà
Elena Deseatnicova
Evgenii Gutu
Francesco Violi
Roberto Carnevale

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