Low-grade endotoxemia and NOX2 in patients with coronary microvascular angina

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 on MVA have not been provided yet.Aims: This study aimed 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 (sNOX2-dp), H 2 O 2 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 sex.Results: Compared with CT, MVA patients had significantly higher values of sNOX2-dp, H 2 O 2 , ET-1, LPS, and zonulin. Conversely HBA and NO bioavailability were significantly lower in MVA patients. Simple linear regression analysis showed that sNOX2 was associated with serum LPS, serum zonulin, H 2 O 2 , and ET-1. Furthermore, an inverse correlation between sNOX2, 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, NOX2 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.

Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards

“…To the best of our knowledge, no description of an association among LPS, NOX2 and endothelial dysfunction has been reported in literature. An association among increased LPS, NOX2 and oxidative stress was already reported in other diseases, such as neurodegenerative ( Loffredo et al, 2020a ), neuropsychiatric ( Loffredo et al, 2020c ) or cardiovascular ( Loffredo et al, 2022b ) disorders.…”

“…Interestingly, the inhibition of NOX-2 decreased LPS-induced superoxide ( Joseph et al, 2017 ). Considering that LPS directly correlates with NOX2 ( Loffredo et al, 2022b ), it could play a role as a trigger of oxidative stress. The high levels of H2O2 together with the low levels of HBA, and the close relation with sNOX2 could indicate that systemic oxidative stress in CP and CAP derive from LPS-induced NADPH oxidase activation as hypothesised by previous studies ( Oliva et al, 2021b ; Petruk et al, 2020 ).…”

Low Grade Endotoxemia and Oxidative Stress in Offspring of Patients with Early Myocardial Infarction

“…Previous studies showed that LPS was increased in the systemic circulation of adult patients with acute myocardial infarction [ 12 , 22 ] and coronary microvascular angina [ 16 ].…”

“…By binding to TLR4, LPS prompts the intracellular transcription of inflammatory pathways and NADPH oxidase activation [ 14 , 15 ], resulting in platelet activation, thrombosis and atherosclerosis [ 12 , 16 ].…”

Gut dysbiosis-derived low-grade endotoxemia: A common basis for liver and cardiovascular disease

“…The relationship between endothelial damage and endotoxemia has been investigated by Loffredo et al [55] who reported elevated LPS levels in patients with microvascular angina, which correlated inversely with serum nitric oxide and directly with serum endothelin 1. Similarly, enhanced LPS levels have been detected in patients with stable angina and myocardial infarction with a gradient increase from stable to unstable disease.…”