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

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.